Clinicopathological Features Research Articles

Cost-benefit analysis and short-term outcomes after implementing an ERAS protocol for colorectal surgery: a propensity score-matched analysis.

Enhanced Recovery After Surgery (ERAS) has become increasingly popular in the post-operative management of abdominal surgery. Published data suggest that patients on ERAS protocols have fewer minor and major complications, and highlight a reduction in medical morbidity (such as urinary and respiratory infections). Limited data is available on surgical complications. The aim of the study was to evaluate the impact of the ERAS protocol on post-operative complications and length of hospital stay. Furthermore, we aimed to determine the impact of this protocol on cost-effectiveness. From January 2016 to December 2022, 532 colectomies for colorectal cancer (CRC) were performed. A prospective observational study was conducted in a tertiary hospital on the cohort of patients, aged 18years and older, operated on for non-urgent colorectal cancer. The impact on post-operative complications, hospital stay and economic impact was analysed in two groups: patients managed under ERAS and non-ERAS protocol. A propensity score-matching analysis was performed between the two groups. After propensity score matching 1:1, each cohort included 71 patients, and clinicopathological characteristics were well balanced in terms of tumour type, surgical technique and surgical approach. ERAS patients experienced fewer infectious complications and a shorter postoperative stay (p < 0.001). In particular, they had an 8.5% reduction in anastomotic dehiscence (p = 0.012) and surgical wound infections (p = 0.029). After analysis of medical complications, no statistically significant differences were identified in urinary tract infections, pneumonia, gastrointestinal bleeding or sepsis. ERAS protocol was more efficient and cost-effective than the control group, with an overall savings of 37,673.44€. The implementation of an enhanced recovery protocol for elective colorectal surgery in a tertiary hospital was cost-effective and associated with a reduction in post-operative complications, especially infectious complications.

Stratified Mucin-producing Lesions of the Anus

Primary anal cancers are rare and typically driven by high-risk human papillomavirus (HPV) infection. Though squamous cell carcinoma is most common, a spectrum of HPV-related nonsquamous anogenital neoplasms with similarities to cervical stratified mucin-producing carcinoma has been reported. In this study, we mined our institutional archives to characterize the clinicopathologic features of this emerging entity. Six cases were identified from the files at 2 institutions, including 4 cases of invasive stratified mucin-producing carcinoma and 2 stratified mucin-producing intraepithelial lesions (SMILE). Four patients were women, and the mean age was 70 years. Patients presented with rectal/anal mass or polyp, rectal bleeding or pain, weight loss, or at the time of screening colonoscopy. Tumors displayed histologic features as described in the gynecologic tract. Cases of invasive stratified mucinous carcinoma showed infiltrative tumor nests with variable intracytoplasmic mucin, peripheral palisading, prominent apoptosis, and neutrophilic infiltrate. One invasive stratified mucinous carcinoma associated with high grade glandular dysplasia, whereas 1 SMILE was next to conventional low-grade squamous intraepithelial lesion. All lesions stained with p16 showed block-like p16 expression. HPV in situ hybridization was performed in 5 cases, 4 of which were positive; one was interpreted as equivocal. Follow-up information, available in 4 patients, revealed 1 local recurrence followed by death due to unrelated causes in a patient with invasive stratified mucin-producing carcinoma. We report the first series of HPV-associated primary anal stratified mucin-producing neoplasms analogous to those seen in the gynecologic tract, further broadening the spectrum of HPV-related anal neoplasia.

Adult Prostate Sarcoma: Demographics, Treatment Patterns, and Survival.

This study aimed to examine clinicopathologic characteristics, treatment patterns, and survival rates in a contemporary population-based cohort of adult prostate sarcoma patients. In the Surveillance, Epidemiology, and End Results database (2004-2020), adult patients with prostate sarcoma were identified. Descriptive statistics, Kaplan-Meier analyses, smoothed cumulative incidence plots, and Cox regression models were used. Of 125 patients, 45 (36%) harbored leiomyosarcoma, 17 (14%) had rhabdomyosarcoma, 15 (12%) had stromal sarcoma, 17 (14%) had sarcoma not otherwise specified (NOS), and 31 (25%) had other sarcoma subtypes. Metastatic stage was most common in the rhabdomyosarcoma patients (44%) and least common in the leiomyosarcoma (21%) and stromal sarcoma (20%) patients. Most of the rhabdomyosarcoma patients received the combination of systemic and radiation therapy with (24%)or without radical surgery(35%), whereas most of the leiomyosarcoma and stromal sarcoma patients underwent radical surgery with (22 and 13%) or without (22 and 47%) radiation. In the overall population, the median overall survival was 27months. The 5-years overall versus cancer-specific versus other-cause mortality rates were respectively 71 versus 58 versus 13%. In the multivariable Cox regression models, the highest overall mortality was exhibited by the patients with metastatic disease (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.55-5.31; p < 0.001) or unknown disease stage (HR 2.94; 95% CI 2.20-7.21; p = 0.019). Conversely, of all the histologic subtypes, only stromal sarcoma distinguished itself by lower overall mortality (HR 0.41; 95% CI 0.18-0.96; p = 0.039). Four major histologic subtypes were identified. Among most adult sarcoma patients, treatment patterns vary according to histology, from multimodal therapy to radical prostatectomy alone. These treatment differences reflect equally important heterogeneity in survival patterns.

Clinicopathological Characteristics and Outcome of very Young Breast Cancer Patients at a Referral Center

Clinicopathological Characteristics and Outcome of very Young Breast Cancer Patients at a Referral Center

Association between pathological T1 colorectal cancer with lymphoid follicular replacement and risk of lymph node metastasis

AbstractBackground and AimEndoscopic resection (ER) is widely performed to treat early colorectal cancer. However, additional surgery for pathological T1 colorectal cancer (pT1CRC) after ER is controversial because of the imprecise prediction of lymph node metastasis (LNM). Recently, several patients of pT1CRC with lymphoid follicular replacement (LFR) without LNM have been reported. This study aimed to investigate the clinicopathological features and risk of LNM in patients with pT1CRC with LFR.MethodsWe retrospectively analyzed patients who underwent ER or surgical resection and were diagnosed with pT1CRC between January 2010 and December 2020. We defined pT1CRC with LFR as the replacement of a part of the lymphoid follicular component within the submucosal area by adenocarcinoma, with no invasion into other submucosal areas.ResultsAmong the 600 eligible patients, the incidence rate of pT1CRC with LFR was 6.7% (40/600). Patients with pT1CRC with LFR represented 14.3% (37/258) of the endoscopically treated patients and 0.9% (3/342) of the surgically treated patients. For patients with pT1CRC with LFR, 80.0% (32/40) had flat and depressed lesions, and 35.0% (14/40) had submucosal invasion depth ≥1000 μm. Patients with pT1CRC with LFR had negative lymphovascular invasion, differentiated type, and budding grade 1. In the median follow‐up of 61 months, patients with pT1CRC with LFR had no LNM.ConclusionsThe presence of LFR in pT1CRC may be associated with a low risk of LNM. In patients with pT1CRC with LFR, follow‐up without additional surgery is possible even if the submucosal invasion depth is ≥1000 μm.

Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression

Abstract Background Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers. Methods We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features. Result CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P &amp;lt; .001), but there was no correlation with age, sex, or stage (P &amp;gt; .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P &amp;lt; .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival. Conclusion This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.

Abstract C149: Relationship between PD-L1 expression and clinicopathological characteristics in Hispanic/ Latino women with breast cancer

Abstract Background: Programmed death ligand 1 (PD-L1) expression in breast cancer serves as a prognostic marker, particularly in aggressive subtypes like triple-negative breast cancer (TNBC), where it helps in predicting response to immune checkpoint inhibitors and guides immunotherapy use. Although several studies have assessed the prevalence of PD-L1 expression in breast cancer, data from the Hispanic population, especially in Latin American countries, is lacking. This study evaluates PD-L1 expression and its correlation with pathological features in Colombian women. Methods: Women with breast cancer tested for PD-L1 were selected from the archives of the Oncologic Pathology Department at the National Cancer Institute of Colombia from September 2021 to May 2024. Information from their pathology reports was extracted, and correlation analyses were carried out using Fisher's exact test Results: A total of 60 reports were screened, comprising 56 cases of ductal invasive breast carcinoma and 1 case of lobular invasive breast carcinoma. 48 individuals were tested using the PD-L1 22C3 antibody, with 41.67% of them being positive for PD-L1 expression. Among the 48 tumors tested with 22C3, 35 cases were classified as TNBC, and 13 cases corresponded to luminal B subtype with a low positive expression (1-10%) of estrogen receptors. The percentage of positive PD-L1 cases was 37.14% for TNBC and 53.85% for the luminal B subtype. Furthermore, 5 HER2-low cases were identified with 2 of them being positive for PD-L1 expression. In the correlation analyses, PD-L1 positive expression was significantly associated with a more aggressive histologic grade compared to PD-L1 negative tumors (p = 0.007). No significant association was found between PD-L1 expression and HR, HER2, or KI67 status, nor with age, necrosis, lymphovascular involvement, perineural invasion, desmoplastic response, or immune cell infiltration. Among the 12 individuals tested for PD-L1 with the SP142 antibody, none showed positive expression, precluding correlation analyses. Conclusion: This study highlights a significant association between PD-L1 expression and aggressive histologic grade in Colombian women with breast cancer. The findings underscore the potential of PD-L1 as a prognostic marker and its relevance in guiding immunotherapy in this population. Further research is needed to explore PD-L1 expression in broader Hispanic groups to better understand its clinical implications. Citation Format: Daniel Mendivelso-González, Patricia López- Correa, Nicolás Prada-Aceros, Alfredo E Romero-Rojas, Rafael Parra-Medina. Relationship between PD-L1 expression and clinicopathological characteristics in Hispanic/ Latino women with breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C149.

Abstract C024: Evaluation of PI3K/AKT/mTOR pathway signaling as a prognostic indicator in Hispanic Mexican women with breast cancer

Abstract Breast cancer (BC) is among the most commonly diagnosed cancer in women and a leading cause of cancer death worldwide. Hispanic/Latina women represent a heterogeneous group with diverse genetic backgrounds, including varying proportions of Native American, European, African and to a lesser extent Asian ancestry. In the US, Hispanic and African American women have lower BC incidence overall yet higher incidence of triple negative breast cancer (TNBC). Furthermore, African American and Hispanic women tend to present with more aggressive disease, at younger ages and worse survival compared to women of European ancestry. These disparities have been attributed to biologic and non-biologic socioeconomic factors. Genomic analyses of Hispanic Mexican (HM) women have revealed specific genetic signatures distinct from those of non-Hispanic women. These variations include AKT kinase mutations activating PI3K/AKT/mTOR signaling pathway and PI3KCA mutations which could potentially benefit from targeted therapies. 4EBP1 phosphorylation by mTORC1 is generally considered a marker of activated mTOR signaling and high levels in tumors associate with worse outcomes in different cancers. To evaluate clinical significance of PI3KCA expression and PI3K/AKT/mTOR signaling, we performed immunohistochemical (IHC) analyses of tissue microarrays (TMA) including 272 BC patient samples from HM women. Protein expression of PI3KCA and p4EBP1 were evaluated quantitatively by receiver operator characteristics (ROC) curves based on area under the curve (AUC) as well as sensibility and specificity. p4EBP1 levels were associated with clinicopathological characteristics. Chi-squared and Fisher’s Exact tests showed higher p4EBP1 expression correlated with estrogen (P=0.001) and progesterone receptor negative BC (P=0.003), TNBC (P&amp;lt;0.001), tumor size (P&amp;lt;0.090), and advanced stage (P&amp;lt;0.001). PI3KCA expression was positively correlated with 4EBP1 expression (P=0.044) as shown by Mann Whitney U tests; but PI3KCA lacked prognostic value after screening through ROC curves. However, uni- and multi-variate Cox regression analyses did show that increased 4EBP1 expression correlates with worse OS. Overall, our study indicates that higher p4EBP1 expression is an independent prognostic factor of worse OS in BC patients. The activation of 4EBP1 may result from several upstream oncogenic alterations or mutations, representing a potential therapeutic target and biomarker. Further research is necessary to better define biological differences in Hispanic women to advance understanding and targeting of health disparities. [Funded by California Breast Cancer Research Program Idea Award B27IB3869, JCCC Breast Cancer Award, Hickey Family Foundation, NCI U54 CA143930, Team Research Grant, UCLA TDG, CIRM DISC2-14166]. Citation Format: Mario Morales Martinez, Giovanny Soca-Chafre, Altagracias Maldonado-Valenzuela, Clara M Rivera-Pazos, Gabriela Antonio-Andres, Mayra Montecillo-Aguado, Georgina Rocha-Lopez, Berenice Alcala-Mota-Velazco, Anel Gomez-Garcia, Madhuri Wadehra1, Richard J Pietras, Sergio Gutierrez-Castro, Sara Huerta-Yepez, Diana Marquez-Garban. Evaluation of PI3K/AKT/mTOR pathway signaling as a prognostic indicator in Hispanic Mexican women with breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C024.

Abstract C120: Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities

Abstract Black persons have the highest mortality rates of both cervical cancer (CC) and pancreatic ductal adenocarcinoma (PDAC) in the United States. Differences in access to quality healthcare and socioeconomic status contribute to these cancer health disparities as well as ancestry and biology. In other cancer types, differences in the inflammatory tumor landscape across races and ancestral populations have been reported. However, the inflammatory tumor microenvironment (TME) as it relates to CC and PDAC health disparities is not well defined. Black patients are often underrepresented in PDAC studies. Meanwhile, CC health disparities studies primarily investigate socioeconomic status, screening, and vaccination rates. Therefore, we aim to characterize the inflammatory TME in these two cancer types with the long-term goal of informing prevention, prognostic, and therapeutic strategies. Clinicopathological characteristics were compared between Black (n = 144) and White (n = 198) patients with CC who received care at Johns Hopkins Medicine between 1995 and 2019. Surgically resected formalin-fixed paraffin embedded (FFPE) CC tissue samples were obtained from Non-Hispanic Black (n = 10), Non-Hispanic White (n = 10), Hispanic Black (n = 5), and Hispanic White (n = 5) women matched on grade, age, and subtype. Tissue microarrays (TMAs) were constructed using archival surgically resected FFPE PDAC tissues from Black (n = 45) and White (n = 45) patients, matched on sex, age, stage, and time of surgery. Multiplexing immunohistochemistry (mIHC) was used to assess markers for i) T cells (CD3, CD8, CD4, FoxP3), M2 macrophages (CD163), mast cells (Tryptase), and fibroblasts (FAP) in PDAC tissues and ii) B cells (CD79A), T cells (CD3, CD8, CD4, FoxP3), plasma cells (CD138/syndecan-1), programmed death-ligand 1 protein (PD-L1), macrophages (CD68, CD163), natural killer cells (NKP46/CD56/CD16), neutrophils (CD66ce), and mast cells (Tryptase) in CC tissues. HALO Image Analysis Platform (version 3.6.4134.137; Indica Labs) was used to quantify marker expression. GraphPad Prism Software (version 10.0.03), was used for graphing and statistical analysis. Squamous cell CC was the most frequent histological subtype in both Black (68%) and White (44%) women. Progression through treatment was more common among Black women (24%) compared to White women (7%). CD163+ M2 macrophages were significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0435), and in tumors from Black women compared to White women (p = 0.0067). FAP+ fibroblasts were also significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0001) and in tumors from Black women compared to White women (p = 0.0013). CD8+ cytotoxic T cells and FoxP3+ regulatory T cells were comparable between races. We observed differences in macrophage and fibroblast distribution between races supporting the effort for future studies that examine the significance of characterizing the TME to address cancer health disparities. Citation Format: Jelani Jarrett, Jae W Lee, Ali Dbouk, Vahinipriya Manoharan, Kennedy Rains, Terri Mason, Kimberly Levinson, Laura D Wood, Michael G Goggins, Janielle P Maynard. Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C120.

Abstract C037: Inflammatory breast cancer by metastatic status: Racial and ethnic and socioeconomic disparities in receipt of treatment

Abstract Background: Inflammatory breast cancer (IBC) is a relatively rare but aggressive type of breast cancer. Racial and ethnic minority patients are disproportionately affected by IBC and often face barriers to accessing cancer care and services. However, racial and ethnic disparities in receipt of treatment are not well defined among patients with IBC by metastatic status. Methods: We analyzed data from patients with IBC in the 2004-2020 U.S. National Cancer Database. Five treatment modalities were assessed: hormone therapy, chemotherapy, radiotherapy, surgery, and trimodal therapy. Metastatic status was dichotomous as “metastatic/non-metastatic.” Racial and ethnic groups included Asian or Pacific Islander, American Indian, Alaska Native, or Other, Black, Hispanic, and White. Separate logistic regression models were fit, adjusting for sociodemographic and clinicopathological characteristics, stratified by metastatic status. Adjusted odds ratios (aOR) and 95% CIs were calculated. Results: Of 33,376 patients with IBC (mean age 58 years [SD=14]), most (70.6%) identified as White, followed by 18.1% as Black, 7.0% as Hispanic, 2.5% as Asian or Pacific Islander, 1.8% as American Indian, Alaska Native, or Other; and 32.5% were metastatic. In the non-metastatic cohort, Black (72.7%; aOR 0.79, 95% CI: 0.63-0.98) or Asian or Pacific Islander (74.8%; aOR 0.59, 95% CI: 0.38-0.90) patients had lower odds of receiving hormone therapy than White patients (78.0%). Compared with White patients, Black patients had a lower likelihood of receiving chemotherapy (89.1% vs. 89.5%; aOR 0.67, 95% CI: 0.53-0.86), surgery (78.4% vs. 85.3%; aOR 0.65, 95% CI: 0.55-0.77), or trimodal therapy (81.5% vs. 87.3%; aOR 0.61, 95% CI: 0.49-0.76). American Indian, Alaska Native, or Other (65.0%; aOR 0.64, 95% CI: 0.42-0.97) and Black (63.6%; aOR 0.71, 95% CI: 0.61-0.82) patients had lower odds of receipt of radiotherapy than White patients (70.6%). In the metastatic cohort, Black patients had a lower likelihood of receiving hormone therapy (55.2% vs. 63.5%; aOR 0.61, 95% CI: 0.48-0.78), chemotherapy (78.7% vs. 78.2%; aOR 0.75, 95% CI: 0.60-0.95), surgery (28.2% vs. 35.1%; aOR 0.68, 95% CI: 0.56-0.82), or trimodal therapy (30.4% vs. 40.4%; aOR 0.63, 95% CI: 0.48-0.82) than White patients. There were no statistically significant differences in receipt of treatment between White and other racial and ethnic patients with metastatic IBC. Furthermore, we observed significantly differential rates of treatment receipts by socioeconomic factors including median household income quartile, insurance coverage, and facility type. Conclusions: In this study of a large U.S. national IBC patient cohort, racial and ethnic minority patients were less likely than White patients to have received treatment for IBC, with Black patients being the most affected. Our findings highlight racial and ethnic disparities and socioeconomic inequities in treatment receipts, suggesting the need for oncology programs to improve equitable care access and reduce these disparities in the IBC population. Citation Format: Jincong Q. Freeman, Jared H. Hara, Olasubomi J. Omoleye. Inflammatory breast cancer by metastatic status: Racial and ethnic and socioeconomic disparities in receipt of treatment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C037.

Abstract C094: Differential expression analysis with transcriptome data in FFPE samples from Colombian patients with colorectal cancer

Abstract Introduction: Colorectal cancer (CRC) is a significant public health issue in Colombia, It occupies third place in incidence and ranking as the fifth leading cause of cancer-related deaths. Understanding the sociodemographic, clinicopathological, and molecular characteristics of CRC patients is crucial for prognosis, effective management, and treatment. Several molecular alterations and clinicopathological variables have been associated with the prognosis of the disease in different populations; However, we do not know if there are differentially expressed genes specific to Colombian population that are associated with CRC prognosis. Objective: Perform differential expression analysis using RNA-seq data obtained from formalin-fixed paraffin-embedded (FFPE) tissue samples from Colombian patients with CRC. Methodology: For this preliminary analysis were included 5 patients diagnosed with CRC between 2010-2014 at Instituto Nacional de Cancerologia from Colombia. From each patient, formalin-fixed and paraffin-embedded (FFPE) samples of tumor tissue and non-tumor tissue from the surgical remnant were obtained. Extracted RNA was used to perform whole-genome RNA sequencing (RNA-seq) at a depth of 100X. Bioinformatic analysis was performed using Fastqc, Cutadapt, Ribodetector, and STAR on a Linux server. The DESeq2 package in RStudio was used to perform the differential expression analysis between tumor samples vs. non-tumorous. A significant differential expression was considered using an FDR-adjusted p ≤0.05 and a log fold change of 2. Results and discussion: A list of 18 differentially expressed genes was obtained which 5 underexpressed stand out: B3GNT6 (LFC:-10.66; padj=0.0093), ITLN1 (LFC:-6.23; padj=0.0231), NR3C2 (LFC:-3.34; padj=0.0231), NLGN1 (LFC:- 0.46; padj=0.0301), CEACAM7 (LFC:-5.91; padj= 0.0301); and one overexpressed gene: RPL9 (LFC:5.44; padj=0.0267). These genes have been previously characterized and associated with the progression and prognosis of this disease in other populations. Conclusions: 6 differentially expressed genes were found using RNA-seq in FFPE samples. These genes have been associated with CRC progression and prognosis in previous studies, but have not been evaluated in the Colombian population. From this perspective, we propose to continue with the analysis by increasing the number of samples and evaluating their association with the different clinicopathological variables and their impact on the prognosis of the disease. Citation Format: Wendy J. Montero Ovalle, Silvia J Serrano Gómez, Diego F Ballen Lozano. Differential expression analysis with transcriptome data in FFPE samples from Colombian patients with colorectal cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C094.

Magnetic resonance imaging and clinicopathological findings of primary hepatic angiosarcoma.

To investigate the magnetic resonance imaging (MRI) and clinicopathological features of primary hepatic angiosarcoma (PHA) and enhance preoperative diagnosis. MRI and clinicopathological information of 12 cases proved PHA were reviewed. Summarize the MRI characteristics of PHA combined with literature reviews. Among 12 cases (6 males and 6 females; age range, 23-70 years; mean, 53.3 years), one presented as a large mass, two as a diffuse infiltrating tumor, and nine as a mixed pattern of large masses with multiple nodules, all involving both lobes of the liver and ranging from 0.1cm to 11cm in diameter. A total of 63 lesions were analyzed, including 21 masses and 42 nodules. 13 masses (61.9%) demonstrated intratumoral hemorrhage. 18 masses (85.7%) demonstrated heterogeneous patchy, ring-shaped, septate, or irregular shaped enhancing foci on late arterial phase (LAP). On dynamic contrast-enhanced MRI (DCE-MRI), 14 masses (66.7%) showed a centripetal or centrifugal pattern of incomplete progressive enhancement. 6 nodules (14.3%) appeared intratumoral hemorrhage. 31 nodules (73.8%) showed no enhancing foci on LAP images and 27 nodules (64.3%) showed enhancement pattern of complete filling, either centripetal or centrifugal pattern. Moreover, 12 cases (100%) exhibited prominent vessels within or adjacent to at least one lesion. PHA exhibits diverse appearances on MRI. Typical MRI signs include multifoci with intratumoral hemorrhage, prominent vessels within or adjacent to the foci, as well as varied degrees of progressive enhancement with incomplete filling in dominant masses of PHA.

Abstract C106: Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos

Abstract Introduction: Colorectal cancer (CRC) remains a significant public health challenge, representing the second leading cause of cancer-related mortality in the United States. Although mortality rates have generally decreased, the Hispanic/Latino (H/L) population in the Los Angeles area still experiences mortality rates up to 20% higher than those of their Caucasian American counterparts. Additionally, they are often diagnosed at a younger age and with more advanced disease stages, highlighting significant disparities in CRC outcomes. Currently, there are limited studies integrating clinical and multi-omics data from H/L populations, which are crucial for understanding the implications of colorectal tumorigenesis and addressing these disparities effectively. Methods: Clinical and genomic sequencing data were obtained from 60 primary CRC Tumor/Normal (T/N) samples within the Hispanic/Latino (H/L) population in the Los Angeles area through the PE-CGS network. For comparison, we analyzed 3,578 samples from non-Hispanic Whites (NHW) obtained from public databases. Additionally, we retrieved three CRC samples with spatial transcriptomic (ST) data from the 10xGenomics database. Using Whole Exome and RNA sequencing data, we performed somatic mutations, somatic copy number alterations (SCNAs), differential gene expression, cellular pathways, gene fusions, and global &amp; local genomic ancestry analyses. The ST data underwent analysis utilizing newly released bioinformatics tools. Clinical and genomic data were integrated. Results: In these studies, distinct Amerindian (AMR) genomic ancestry proportion, age at diagnosis, and tumor localization patterns were observed, alongside significant mutations in key genes such as APC, TP53, and KRAS. The studies revealed evident cancer heterogeneity, influenced by factors such as mutation type, microsatellite instability, tumor subsite, and ethnicity. Additionally, several previously well-defined SCNAs were detected in the majority of tumors. Comparative analysis of gene expression and cellular pathways between H/L and NHW samples revealed distinct patterns. Furthermore, we identified gene fusions that potentially contribute to oncogenic activity in CRC. Ancestry analysis pointed to a predominant AMR ancestry. Notably, distinct associations of genetic ancestry with CRC tumor clinicopathological characteristics were identified. ST analysis delineated separate cancer, immune, and stroma components within the tumors. Conclusion: Our research has explored the molecular profiling of CRC tumors in H/L patients, providing crucial insights into the characterization of CRC tumors at the DNA and RNA levels, as well as the complex clinical and genomic diversity within our target population. Additionally, it offers valuable insights into the heterogeneity of CRC tumors and the tumor microenvironment. These findings establish the groundwork for subsequent projects, potentially leading to precision medicine approaches. Citation Format: Enrique I. Velazquez-Villarreal, Brigette Waldrup, Yonatan Amzaleg, Yuxin Jin, Mackenzie Postel, Donna Loza, Serina Ovalle, Elizabeth Quino, Carmen Chavez, Julie Culver, Mariana C. Stern, Heinz-Josef Lenz, David W. Craig, John D. Carpten. Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C106.

Risk factors for unclear margin in cold snare polypectomy for colorectal polyp.

Cold snare polypectomy (CSP) is a common, simple, and safe procedure; however, it has a high rate of unclear margins. We analyzed the risk factors for unclear margins of colorectal polyp. We retrospectively investigated colorectal polyps treated with CSP between July 2021 and July 2022, excluding those that could not be retrieved or pathologically nonneoplastic and hyperplastic polyps without margin evaluation. The clinicopathological features and risk factors for unclear margins were analyzed. Furthermore, the polyps were divided into two groups: those resected by experts and those resected by trainees. A 1 : 1 propensity score matching was performed. After matching, the risk factors for unclear margins in each group were analyzed as secondary outcomes. We analyzed 237 patients with 572 polyps; the margins were negative in 58.6% (negative group) and unclear in 41.4% (unclear group). The unclear margin was significantly higher at straddling folds (P = 0.0001), flexure points (P = 0.005), and in the procedures performed by trainees (P < 0.0001). Altogether, 198 propensity score matched pairs were explored for secondary outcomes. There were no significant differences in risk factors for unclear margins in the expert group, while in the trainee group, the unclear margin was significantly higher at the straddling folds (P = 0.0004) and flexure points (P = 0.005). We demonstrated that straddling folds, flexure points, and procedures performed by the trainees were significant risk factors for unclear margins, and we hypothesized that the rate of unclear margins will reduce as the trainees accumulate experience at difficult sites.

Expression of Ki-67 in Invasive Breast Carcinoma and Its Correlation With Different Clinicopathological Features.

Introduction Worldwide, breast cancer is still the most common cancer that affects women. Breastcancer prognosis is based on a number of clinical and pathological indicators. Further features are needed to predict early metastasis andprognosis of patients with breast carcinoma, as the current pathological characteristics, such as tumor differentiation, vascular infiltration, and TNM (tumor, node, and metastasis) staging, cannot fully describe the early metastatic biological behavior in breast carcinoma. High Ki-67 expression is seen to be associated with worse survival in cancer patients. Hence, this study was conducted to study the utility of Ki-67as a prognostic marker in invasive breast carcinoma and its association with known clinicopathological factors. Methodology The study was a hospital-based cross-sectional study carried out in the Histopathology Section of the Department of Pathology, Shri BM Patil Medical CollegeHospital and Research Centre, Bijapur Lingayat District Education (BLDE) (Deemed to be University), Vijayapura. The study was conducted between September 1, 2022, and April 30, 2024. The study population consisted of 55 cases of mastectomy specimens of primary breast cancer admitted to our hospital. Data regarding the patient's age, tumor size, histological type, histological grade, lymph node status, and vascular invasion were noted from medical records. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu (HER2/neu) proto-oncogene, and Ki-67 markers was performed according to standard protocol. The relationship of Ki-67with these clinicopathological parameters was analyzed statistically. Results In the current study, high-grade Ki-67 nuclear positivity was seen in 30 cases out of 55 cases, and low-grade Ki-67 was seen in the remaining 25 cases. The association of Ki-67 with tumor size and histological grade showed statistical significancewith a p-value of less than 0.05 and 0.001, respectively. However, no statistical significance was seen with lymph node status, vascular invasion, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu)proto-oncogene status with p-values greater than 0.05. Conclusion The expression of Ki-67 was statistically significant with histological grading and tumor size in our study. Immunohistochemical determination of the Ki-67 proliferation index should be performed in routine cases of breast cancerto obtain clinically useful information on tumor aggressiveness as reflected in their proliferative rate. Hence, Ki-67 can be used as a predictive and prognostic marker in managing breast cancer patients.

Mesenchymal stem cells in tumor microenvironment: drivers of bladder cancer progression through mitochondrial dynamics and energy production

Mesenchymal stem cells (MSCs) in tumor microenvironment (TME) are crucial for the initiation, development, and metastasis of cancer. The impact and mechanism of MSCs on bladder cancer are uncertain. Here we analyzed 205 patient samples to explore the relationships between tumor-stroma ratio and clinicopathological features. A co-culture model and nude mouse transplantation were used to explore the biological roles and molecular mechanisms of MSCs on bladder cancer cells. We found that a high tumor-stroma ratio was significantly associated with a larger tumor size and higher T stage, pathological grade, number of vascular invasions, and poor overall survival. MSCs in TME promoted the ability of bladder cancer cells to proliferate, migrate, and invade in vitro and in vivo. Next, we demonstrated that MSCs enhance mitochondrial autophagy and mitochondrial biogenesis of bladder cancer cells, and increase energy production, thereby promoting bladder cancer cell progression. Kynurenine (Kyn) produced by MSCs could enhance mitochondrial function by activating the AMPK pathway. IDO1 inhibitor could reverse the tumor‑promoting effects of MSCs in vitro and in vivo. Our results demonstrated that tryptophan metabolites Kyn of MSCs in TME could enhance mitochondrial function by activating the AMPK pathway, thereby promoting bladder cancer cell progression.

Association of MORC2 expression with progression-free survival in cervical cancer patients treated with concurrent chemoradiotherapy.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.

Analysis of HER2-Low Breast Cancer in Aotearoa New Zealand: A Nationwide Retrospective Cohort Study.

To perform the first national analysis of demographic and clinicopathological features associated with the HER2 positive, HER2-low, and HER2-zero invasive breast cancers in New Zealand. The study will reveal the proportion of women who may benefit from new HER2-targeted antibody drug conjugate (ADC) therapies. Utilising data from Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), the study analysed data from women diagnosed with invasive breast cancer over a 21-year period. The HER2 status of tumours was classified into three categories-HER2-zero, HER2-low, HER2-positive. From 2009-2021, 94% of women underwent HER2 testing, with 14% diagnosed with HER2-positive breast cancer. For advanced-stage disease, 38% of those formerly classified as HER2-negative were reclassified as HER2-low. Including HER2-positive breast cancers, this indicates that 60% of women with advanced breast cancer may potentially benefit from the new HER2-directed ADCs (approximately 120 women per year). The findings suggest a significant proportion of women with invasive breast cancer in New Zealand could benefit from new HER2-targeted treatments. There is a need to standardise HER2 testing to enhance personalised treatment and improve outcomes.

Clinicopathological and prognostic features of colorectal mucinous adenocarcinomas: a systematic review and meta-analysis

BackgroundMany studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs).MethodsThe meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC.ResultsFifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99–1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79–1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03–1.04, P < 0.01), but not DFS in CRCs (HR = 1.01,95% CI: 0.88- 1.17, P = 0.85). Subgroup analysis found that MAC was obviously correlated with OS in patients with different recruitment time, with tumor located in rectum, from different regions, with different sample sizes and with TNM stage in II, and calculated by different data types(P < 0.01).ConclusionsThis study shows that MAC displays obviously different clinicopathological features compared with AC. And MAC has a poor OS relative to AC but the DFS was comparable.

Driver gene alterations in NSCLC patients in southern China and their correlation with clinicopathologic characteristics.

In this study, we aimed to explore the relationship between clinicopathological features and driver gene changes in Chinese NSCLC patients. Amplification refractory mutation system PCR was used to detect the aberrations of 10 driver oncogenes in 851 Chinese NSCLC patients, and their correlation with clinicopathological characteristics was also analyzed. Moreover, three models of logistic regression were used to analyze the association between histopathology and EGFR or KRAS mutations. The top two most frequently aberrant target oncogenes were EGFR (48.06%) and KRAS (9.51%). These were followed by ALK (5.41%), HER2 (2.35%), MET (2.23%), RET (2.11%), ROS1 (1.88%), BRAF (0.47%), NRAS (0.24%), and PIK3CA (0.12%). Additionally, 11 (1.29%) patients had synchronous gene alterations in two genes. The main EGFR mutations were exon 21 L858R and exon 19-Del, which accounted for 45.97% and 42.79% of all EGFR mutations, respectively. Logistic regression analysis showed that the frequency of EGFR mutations was positively correlated with women, non-smokers, lung adenocarcinoma, and invasive non-mucinous adenocarcinoma (IA), and negatively correlated with solid nodule, micro-invasive adenocarcinoma, and solid-predominant adenocarcinoma. KRAS mutations were positively associated with men and longer tumor long diameters and negatively correlated with lung adenocarcinoma (P < 0.05 for all). Our findings suggest that the EGFR mutation frequency was higher in women, non-smokers, lung adenocarcinoma, and the IA subtype in lung adenocarcinoma patients, while the KRAS mutation rate was higher in men and patients with longer tumor long diameter and lower in lung adenocarcinoma patients.