Specific Histological Subtypes Research Articles

Abstract PO3-08-05: Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes

Abstract Background: Special histologic subtypes of breast cancer, including mucinous and tubular, account for 25% of all invasive breast cancers. Multigene tests (MGT) play a crucial role in guiding adjuvant chemotherapy and predicting prognosis for the patients with Hormone receptor-positive HER2-negative breast cancer. This research aims to examine the results of multigene tests for special histologic subtype patients and review the prognosis of each group. Methods: A retrospective analysis was conducted on data from 133 patients with special histologic subtypes of breast cancer who underwent surgery at Severance Hospital between November 2013 and December 2022. Each patient underwent one type of MGT, including Oncotype Dx, MammaPrint, or EndoPredict. Patients were grouped in two groups according to histologic types, based on WHO classification. Favorable types consist of type A mucinous carcinoma, pure tubular carcinoma, invasive solid papillary carcinoma, encapsulated papillary carcinoma with invasion, invasive cribriform carcinoma, secretory carcinoma, and invasive carcinoma with apocrine differentiation. Unfavorable types included type B mucinous carcinoma, mucinous carcinoma with micropapillary feature or neuroendocrine differentiation, mixed IDC, ILC or invasive micropapillary carcinoma, mixed invasive solid papillary carcinoma, mixed invasive papillary carcinoma, and mixed invasive cribriform carcinoma with IDC. Results: Patients with favorable types accounted for 42.86% (57 patients), while patients with unfavorable types accounted for 57.14% (76 patients). Patients with unfavorable histologic subtypes of breast cancer tended to have a higher incidence of high-risk results in MGT, as well as a greater prevalence of multiple (multifocal, multicentric) cancer and higher histologic grade. In multivariate analysis using logistic regression, unfavorable types showed a significantly high ratio of having high risk on MGT compared to the favorable type (OR = 4.327, 95% CI 1.210 – 15.475, p-value = 0.024). Moreover, overall survival in unfavorable histologic types showed a statistically significant difference between high-risk and low-risk in Kaplan-Meier survival analysis (p-value = 0.001). Conclusions: Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions. Citation Format: Seung Hye Yang, Jee Hyun Ahn, Suk Jun Lee, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-05.

Abstract PO1-28-10: Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy

Abstract Introduction International guidelines recommend chemotherapy for most patients with stage I triple negative breast cancer (TNBC), except for special histological subtypes. However, the absolute benefit of systemic treatment for all stage I TNBC patients is not well known and no tools are yet available to select patients with an excellent prognosis for whom the chemotherapy can be safely omitted. High levels of stromal tumor infiltrating lymphocytes (sTILs) are strongly associated with favorable prognosis in TNBC, however, data solely focusing on patients with stage I TNBC who did not receive chemotherapy are lacking. Methods Patients with pT1N0M0 TNBC diagnosed between 2005 and 2015 not treated with (neo)adjuvant chemotherapy were identified from the nationwide Netherlands Cancer Registry (NCR) and linked to the national pathology database (PALGA). Newly sectioned hematoxylin & eosin (H&E) slides were used for central review of the histology and sTILs scoring following the International TIL working group guidelines (www.tilsinbreastcancer.org). Cause of death was provided by Statistics Netherlands (CBS). Primary endpoint was breast-cancer specific survival (BCSS) at 5-, 10- and 15-years for prespecified sTILs cut-offs of 30%, 50% and 75% sTILs. Results sTILs were evaluated for 1,041 patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. Mean age at diagnosis was 64.4 years [range 26 – 96] and median sTILs value was 5%. Most tumors (91.5%) were invasive ductal adenocarcinomas of no special type (NST) and 6.6% were of histological special types. In 52% of the patients the tumor was >1cm (pT1cN0). Median follow-up was 9.4 years in which 335 patients had died, of whom 107 due to breast cancer. Patients with pT1abN0 tumors had a favorable prognosis compared with patients with a pT1cN0 tumor (HR 0.47, CI 0.32- 0.72). 10-year BCSS in patients with pT1ab was 91.8% and 85.8% in patients with pT1c tumors. In the overall cohort, sTILs-levels of at least 30% were associated with better BCSS compared to sTILs < 30% (HR 0.45, CI 0.26 – 0.77), with 10year-BCSS of 96% and 87%, respectively (table 1). Patients with TNBC of special histological subtype had low sTILs (median 1%). A univariate cox model showed no association between sTILs (continuous) and BCSS in TNBC of special histological subtype (p = 0.56). Next, the prognostic value of sTILs was evaluated separately for pT1ab and pT1c. High sTILs ≥50% were not associated with improved BCSS compared to low sTILs < 50% in patients with pT1ab (HR 1.35, CI 0.65 – 2.82, p = 0.42). In contrast, high sTILs ≥50% showed a strong prognostic importance over low sTILs < 50% (HR 0.27, CI 0.10 – 0.74) in patients with pT1C tumors. We found excellent 10year-BCSS of 95% for patients if sTILs ≥50%, which further increases to 98% with sTILs ≥75% contrasting 10year-BCSS of 83% for patients with sTILs < 30%. Conclusions sTILs-levels provide important prognostic information in patients with stage I TNBC who did not receive (neo)adjuvant chemotherapy. The outcome of patients with pT1c TNBC and sTILs ≥50% was excellent, with 10year-BCSS of 95%, and 98% if sTILs >75%. This large registry study provides a foundation for clinical trials in patients with stage I TNBC with high TILs to prospectively confirm their excellent survival without chemotherapy. Citation Format: Veerle Geurts, Sara Balduzzi, Hugo Horlings, Tessa G Steenbruggen, Sabine Siesling, Sylvia Adams, Gabe Sonke, Roberto Salgado, Marleen Kok. Tumor Infiltrating Lymphocytes identify patients with stage I TNBC with excellent outcome without chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-10.

The Role of Surgery in Pleural Mesothelioma.

Surgery plays a central role in the diagnosis, staging, and management of pleural mesothelioma. Achieving an accurate diagnosis through surgical intervention and identifying the specific histologic subtype is crucial for determining the appropriate course of treatment. The histologic subtype guides decisions regarding the use of chemotherapy, immunotherapy, or multimodality treatment. The goal of surgery as part of multimodality treatment is to accomplish macroscopic complete resection with the eradication of grossly visible and palpable disease. Over the past two decades, many medical centers worldwide have shifted from performing extra-pleural pneumonectomy (EPP) to pleurectomy decortication (PD). This transition is motivated by the lower rates of short-term mortality and morbidity associated with PD and similar or even better long-term survival outcomes, compared to EPP. This review aims to outline the role of surgery in diagnosing, staging, and treating patients with pleural mesothelioma.

Mast cells in meningiomas.

Meningioma represents the most frequent tumor of the central nervous system (CNS). Correlations between thepresence of mast cells (MCs) and grade or other histological features of meningioma are still debated. Our study aimed to better understand the relationship between mast cells and meningiomas and to compare our resultsbased on specific histological subtypes and novel 2021 CNS WHO grading system. We observed some differences as regards the number of MCs and meningioma grade. In low-grade (grade 1) meningiomas, MCs were observed in 7/22 cases, while they were consistently present in all eight high-grade cases (grade 2 and grade 3). Among the grade 1 meningiomas, we observed two "low-positive", two "intermediate-positive", and three "high-positive" cases. Among the group of high-grade meningiomas, the six cases grade 2 were considered as"low-positive", while the two grade 3 cases showed a higher number of MCs and were included in the "intermediate-positive" group. Even though with no statistical significance, due to the low number of cases, ourresults seem to confirm a sort of relationship between meningioma grading and the number of MCs, as demonstrated by the higher percentage of high-grade meningiomas showing MCs infiltrates, compared to low-grademeningiomas.

Immunochemistry-based quantification of tumor-infiltrating lymphocytes and immunoscore as prognostic biomarkers in bladder cancer

BackgroundTumor-infiltrating lymphocytes (TILs) and the derived immunoscore (IS) have gained considerable attention over the last decade as prognostic markers in many solid cancers. However, in bladder cancer (BC), their prognostic value is not clearly established.MethodsThe present study aimed to quantify the TILs rates in BC, assess the derived immunoscore, and investigate their prognostic value. An immunochemistry-based quantification of the different subtypes of TILS was performed on paraffin-embedded blocks from patients with invasive urothelial carcinoma of the bladder. We have assessed the rates of TILs, respectively, on peri-tumoral (PT) and intra-tumoral (IT) areas and calculated for each case the corresponding IS which is the index: CD8+/CD3+ TILs. The IS was then classified as low (I0, I1) or high (I2, I3, I4). We included 30 cases in the analysis.ResultsThe median age of patients was 65 years with a sex ratio of 9. TILs densities and distribution were significantly variable between IT and PT areas CD3+ (p = 0.03) and CD8+ (p = 0.004) with the highest rates on the PT areas. In univariate analysis, a low density of CD8+ TILs was significantly associated with an advanced age (p = 0.05), with the presence of lympho-vascular invasion (p = 0.02) and with the absence of specific histological subtype (p = 0.05). A low immunoscore was significantly associated with the presence of lympho-vascular invasion (p = 0.004). No significant association was found between TILs subpopulations, the IS, and the other clinicopathological and survival data. The overall survival (OS) and disease-free survival (DFS) medians were slightly superior in highly T (CD3+/CD8+)-cell infiltrated tumors as well as tumors with a high IS densities. However, the univariate analysis showed that TILs and immunoscore did not impact overall survival (OS) and disease-free survival (DFS).ConclusionTILs and immunoscore might be effective prognostic tools in BC. However, standardized quantification methods and further investigation on larger samples are highly recommended to definitively attest the prognostic value of TILs and IS in BC.

Construction and validation of log odds of positive lymph nodes (LODDS)-based nomograms for predicting overall survival and cancer-specific survival in ovarian clear cell carcinoma patients.

Ovarian clear cell carcinoma (OCCC) is one of the special histologic subtypes of ovarian cancer. This study aimed to construct and validate log odds of positive lymph nodes (LODDS)-based nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Patients who underwent surgical treatment between 2010 and 2016 were extracted from the Surveillance Epidemiology and End Results (SEER) database and the data of OCCC patients from the First Affiliated Hospital of Dalian Medical University were used as the external validation group to test the validity of the prognostic model. The best-fitting models were selected by stepwise Cox regression analysis. Survival probability was calculated by the Kaplan-Meier method, and the differences in survival time between subgroups were compared using the log-rank test. Each nomogram's performance was assessed by the calibration plots, decision curve analysis (DCA), and receiver operating characteristics (ROC) curves. T stage, distant metastasis, marital status, and LODDS were identified as significant risk factors for OS. A model with four risk factors (age, T stage, stage, and LODDS value) was obtained for CSS. Nomograms were constructed by incorporating the prognostic factors to predict 1-, 3- and 5-year OS and CSS for OCCC patients, respectively. The area under the curve (AUC) range of our nomogram model for OS and CSS prediction ranged from 0.738-0.771 and 0.769-0.794, respectively, in the training cohort. The performance of this model was verified in the internal and external validation cohorts. Calibration plots illustrated nomograms have good prognostic reliability. Predictive nomograms were constructed and validated to evaluate the OS and CSS of OCCC patients. These nomograms may provide valuable prognostic information and guide postoperative personalized care in OCCC.

Are there specific cytologic features that can predict BRAFV600E mutational status of papillary thyroid carcinoma in fine-needle aspiration specimens?

BRAFV600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features. A computerized search for diagnosed PTC surgical pathology cases tested for BRAFV600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAFV600E mutational status and histologic subtypes. Study cohort consisted of 113 cases (74 BRAFV600E mutated, 39 BRAFV600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status. CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.

Prostate cancer (PC) is a common malignancy among elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant of prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in the tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53), and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.

Intraventricular Ependymoma in Pediatric Patients: A Systematic Review of Demographics, Clinical Characteristics, and Outcomes

Background: Intraventricular neoplasms are rare occurrences observed in 5 – 7% of all primary pediatric brain tumors. Pediatric intraventricular ependymomas are a complex subset of these tumors, poorly discussed across the current literature. Although surgery is generally the accepted treatment of choice, information on clinical course and outcomes is limited to heterogeneous case reports and small case series focusing on specific histologic subtypes or ventricular locations. We conducted a systematic review on pediatric intraventricular ependymomas to survey the patient population, tumor characteristics, management strategies, and associated outcomes.
 Project Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting pediatric patients with intraventricular ependymomas. Clinical characteristics, treatment protocols, and outcomes were analyzed.
 Results: A total of 9 studies with 70 patients were included. Most patients were male (54%), diagnosed at a mean age of 7 years (range, 0.2-17), and frequently exhibited nausea and vomiting (38%), headache (31%), and ataxia (25%). Tumors were predominantly located in the fourth ventricle (79%) and most tumors were WHO grade 2 (73%). Mean tumor volume was 3 cm3 (range, 0.1-13.2). Management included surgical resection (96%), radiotherapy (87%), and chemotherapy (38%). Gross total resection was achieved in 69% of cases. Cranial nerve deficit was the most common post-surgical complication (71%). Most common combination of treatment included surgical resection and radiotherapy (53%). Mean overall survival was 50 months in these patients.
 Conclusion/Impact: Pediatric intraventricular ependymomas are rare tumors with limited information on management strategies. The mainstay of treatment is complete surgical resection. Compared to ependymomas, intraventricular ependymomas appear to have a worse overall prognosis.

Management of acral lentiginous melanoma: current updates and future directions.

Acral lentiginous melanoma is a rare subtype of melanoma generally associated with poor outcomes, even when diagnosed at an early stage. The tumor genetic profile remains poorly understood, but it is known to have a suppressed immune environment compared to that of non-acral cutaneous melanomas, which limits therapy options. There is significant attention on the development of novel therapeutic approaches, although studies are limited due to disease rarity. For local disease, wide local excision remains the standard of care. Due to frequent under-staging on preoperative biopsy, wider margins and routine sentinel lymph node biopsy may be considered if morbidity would not be increased. For advanced disease, anti-PD1 monotherapy or combination therapy with anti-PD1 and anti-CTLA4 agents have been used as first-line treatment modalities. Anti-PD1 and anti-CTLA4 combination therapies have been shown to be particularly beneficial for patients with BRAF-mutant acral lentiginous melanoma. Other systemic combination regimens and targeted therapy options may be considered, although large studies with consistent results are lacking. Regional and intralesional therapies have shown promise for cutaneous melanomas, but studies generally have not reported results for specific histologic subtypes, especially for acral melanoma. Overall, the unique histologic and genetic characteristics of acral lentiginous melanoma make therapy options significantly more challenging. Furthermore, studies are limited, and data reporting has been inconsistent. However, more prospective studies are emerging, and alternative therapy pathways specific to acral lentiginous melanoma are being investigated. As further evidence is discovered, reliable treatment guidelines may be developed.

The Clinicopathological Characteristics of Young-Onset Versus Adult-Onset Colorectal Cancer: A Tertiary Hospital-Based Study.

The prevalence of colorectal cancer (CRC) among young individuals is rising worldwide, especially in Malaysia. Investigations are currently employed to distinguish the features of young-onset CRC (YOCRC) from adult-onset CRC (AOCRC). This study aimed to compare the characteristics of patients with YOCRC and AOCRC diagnosed at Hospital Universiti Sains Malaysia (HUSM). This was a retrospective study of CRC cases from January 2013 to December 2021. The details of YOCRC (< 50 years old) and AOCRC (≥ 50 years old) patients were retrieved from the laboratory system and medical records. The Pearson's chi-square test, Fisher's exact test and multiple logistic regression were used to compare the AOCRC and YOCRC cases. Statistical significance was defined at a P-value of ≤ 0.05. The AOCRC (254/319, 79.6%) was more prevalent than YOCRC (65/319, 20.4%), with a predominance of males (53.9%) and Malay sub-population (90.2%). AOCRC and YOCRC shared similarities in left-sided location, high occurrence of adenocarcinoma with moderately differentiated histology and advanced stage of diagnosis. More patients with YOCRC (23.1%) had a family history of cancer than patients with AOCRC. YOCRC also differed from AOCRC by having more specific histological subtypes, such as mucinous adenocarcinoma (15.4%) and signet ring carcinoma (6.2%). In addition, patients with YOCRC commonly presented with a low density of tumour-infiltrating lymphocytes (TILs) (60%). Multiple logistic regression showed a family history of CRC (adjusted odds ratio [AOR] = 3.75, P = 0.003) and histological type (AOR = 15.21, P < 0.001) are more likely to cause YOCRC than diabetes (AOR = 0.06, P < 0.001) and hypertension (AOR = 0.14, P < 0.001) comorbidities, which are associated with AOCRC. Our descriptive study presented the epidemiological and histopathological characteristics of AOCRC and YOCRC in HUSM, providing current information on distinguishing features between the groups.

Prognostic implications of T stage in different pathological types of colorectal cancer: an observational study using SEER population-based data

ObjectivesColorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system’s predictive efficiency. Thus, this study aims to explore the prognostic...

Spatial distribution of histological subtypes of Meningioma: A 14-Year longitudinal study in a developing country

BackgroundMeningiomas are extra-axial tumors that arise from meningothelial cells, accounting for about one-third of primary central nervous system malignancies. While they are often classified by location and histology, the role of the molecular profile in their development and progression is significant. The topographic distribution of meningiomas has not been extensively studied, and it is unclear whether specific histological subtypes have predilection sites. Therefore, this study analyzes the preferred locations of meningiomas according to different biological characteristics and their association with different gradings. MethodsThis is a retrospective chart review of patients in tertiary institutes over 14 years. The data were retrieved from medical and pathological record archives. An association between the biological nature of tumors and the location of meningiomas was analyzed. SPSS version 25 was used to analyze the data. ResultsOut of 272 patients, the predominant location for meningioma distribution was convexity (33.5%), followed by parafalcine (12.5%). WHO Grade I meningiomas were the most common, accounting for 84.2% of all meningiomas. The transitional histological subtype is the common variant (34.6%). The distribution of the histological subtype of meningioma in relation to tentorium was statistically significant. However, that was not the case with the skull base. ConclusionThe spatial distribution of meningiomas within the brain is not uniform. The most frequent locations for meningiomas were found to be convexity and parafalcine. Transitional and fibroblastic meningiomas were the predominant subtypes.

Combination of Genomic Landsscape and 3D Culture Functional Assays Bridges Sarcoma Phenotype to Target and Immunotherapy.

Genomic-based precision medicine has not only improved tumour therapy but has also shown its weaknesses. Genomic profiling and mutation analysis have identified alterations that play a major role in sarcoma pathogenesis and evolution. However, they have not been sufficient in predicting tumour vulnerability and advancing treatment. The relative rarity of sarcomas and the genetic heterogeneity between subtypes also stand in the way of gaining statistically significant results from clinical trials. Personalized three-dimensional tumour models that reflect the specific histologic subtype are emerging as functional assays to test anticancer drugs, complementing genomic screening. Here, we provide an overview of current target therapy for sarcomas and discuss functional assays based on 3D models that, by recapitulating the molecular pathways and tumour microenvironment, may predict patient response to treatments. This approach opens new avenues to improve precision medicine when genomic and pathway alterations are not sufficient to guide the choice of the most promising treatment. Furthermore, we discuss the aspects of the 3D culture assays that need to be improved, such as the standardisation of growth conditions and the definition of in vitro responses that can be used as a cut-off for clinical implementation.

HSP90 expression is associated with outcome in pulmonary carcinoid tumor patients.

Pulmonary carcinoids (PCs) are rare tumors that account for <2% of all lung cancer cases. Patients who undergo resection for PC tumors generally have a favorable prognosis, but there is a risk for late recurrence and distant metastasis. The objective of this study was to identify biomarkers for PC tumors using RNA sequencing and immunohistochemistry. A total of 128 formalin-fixed, paraffin-embedded PC tumor samples from patients surgically treated at Helsinki University Hospital between 1990 and 2013 were analyzed in the study. RNA sequencing was first used to detect genes with higher expression in specific histological subtypes and metastatic and nonmetastatic tumors than in adjacent lung tissue. The diagnostic potential of the biomarkers was assessed using immunohistochemistry. Through gene expression analysis, HSP90AB1 expression was found to be significantly elevated in metastatic PC tumors (P<0.0001). The paralog of the gene, HSP90AA1, was also overexpressed, but the finding was not statistically significant. Through immunohistochemical analysis, HSP90 protein expression was found to be associated with shorter disease-specific survival (DSS) (P=0.009) and increased risk of disease-specific death [hazard ratio (HR) 6.4, 95% confidence interval (CI): 1.3-31.8]. This study confirms that HSP90 has a prognostic role in PC tumors and that inhibition of HSP90 may possess therapeutic potential in the management of PC tumor patients in the future.

Histologic heterogeneity predicts patient prognosis of HER2-positive metastatic breast cancer: A retrospective study based on SEER database.

Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC. HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods. A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy. Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.

The crucial value of serum ferritin in assessing high-risk factors and prognosis for patients with endometrial carcinoma

BackgroundEndometrial carcinoma is a common malignant tumor in female reproductive system. At present, there is no effective and economic prognostic index. This study aimed to investigate the effect of serum ferritin levels on the prognosis of endometrial carcinoma.MethodsData of 367 patients who diagnosed with endometrial carcinoma at the First Affiliated Hospital of Chongqing Medical University between January 2012 and August 2018 was retrospectively analyzed. The prediction accuracy was evaluated by receiver operating characteristics curves and Youden's J statistics. Hosmer–lemeshow test was used to confirm the goodness of fit of the model. The prognostic value of serum ferritin on disease free survival (DFS) and overall survival (OS) of endometrial carcinoma was evaluated by univariate log-rank tests and multivariate cox regression models.ResultsPreoperative high serum ferritin was correlated with older age, high grade, specific histological subtypes and recurrence of endometrial carcinoma (P < 0.05). The DFS and OS of 198 patients with elevated serum ferritin levels were significantly lower than those with low serum ferritin levels (P = 0.001 and P = 0.002, respectively). In multivariate analysis, serum ferritin was an independent prognostic factor for DFS and OS in endometrial carcinoma (P = 0.012, P = 0.028).ConclusionThrough our research, we found that the high expression of serum ferritin level was not only related to low DFS and OS in patients with endometrial carcinoma, but also related to the high-risk factors of endometrial carcinoma recurrence. So serum ferritin levels may be used to predict the poor prognosis of patients with endometrial carcinoma.

REGIONAL DIFFERENCES IN THE SURVIVAL EXPERIENCE OF PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMOURS IN CANADA

Abstract Health care in Canada is delivered on a provincial or territorial level. The objective of our population-based study was to investigate regional differences in survival among Canadians diagnosed with central nervous system (CNS) tumours. We identified 50,670 patients diagnosed with a first-ever primary CNS tumour between 2008 and 2017 with follow-up until December 31, 2017 (excluding Quebec) from the Canadian Cancer Registry linked to vital statistics. We selected the four highest incidence histologies and used Cox proportional hazards regression to estimate hazard ratios (HRs) for regions in Canada (British Columbia, the Prairie provinces, Ontario, the Atlantic provinces, and the Territories) adjusting for sex and tumour behaviour (malignant vs. non-malignant), and stratified by patient age. Ontario was the reference region and had the best survival profile for all histologies investigated. The Atlantic provinces had the highest HR for glioblastomas (HR=1.26, 95% CI:1.18-1.35), gliomas not otherwise specified (NOS) (Overall: HR=1.87, 95% CI:1.43-2.43; Pediatric population: HR=2.86, 95% CI:1.28-6.39) and unclassified tumours (HR=1.95, 95% CI:1.63-2.34). For meningiomas, the Territories had the highest HR (HR=2.44, 95% CI:1.09-5.45) followed by the Prairie provinces (HR=1.52, 95% CI:1.38-1.67). Our findings suggest that regional differences in survival may exist for patients with specific histological subtypes of CNS tumours at the population level. Whether the differential capture of non-malignant tumours across regions, tumour misclassification, or both contributes to the observed regional survival differences warrants further investigation.

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as EOC, and are therefore envisaged as future biomarkers. We present a meta-analysis of available gene expression profiling (microarray and RNA sequencing) studies from EOC patients to identify lncRNA genes with diagnostic and prognostic value. In this meta-analysis, we include 46 independent cohorts, along with available expression profiling data from EOC cell lines. Differential expression analyses were conducted to identify those lncRNAs that are deregulated in (i) EOC versus healthy ovary tissue, (ii) unfavorable versus more favorable prognosis, (iii) metastatic versus primary tumors, (iv) chemoresistant versus chemosensitive EOC, and (v) correlation to specific histological subtypes of EOC. From the results of this meta-analysis, we established a panel of lncRNAs that are highly correlated with EOC. The panel includes several lncRNAs that are already known and even functionally characterized in EOC, but also lncRNAs that have not been previously correlated with this cancer, and which are discussed in relation to their putative role in EOC and their potential use as clinically relevant tools.

Bioinformatics-Based Characterization of ATP-Binding Cassette Subfamily B Member 1 (ABCB1) Gene Expression in Non-Small-Cell Lung Cancer (NSCLC)

P-glycoprotein (P-gp) has been implicated in lung cancer development, disease progression, and patient survival. Changes in the ABCB1 expression level may correlate with tumorigenesis and the formation of multidrug resistance (MDR). In addition, epigenetic modifications such as DNA methylation are involved in the regulation of the transcriptional activity of this gene. Therefore, we focused on an analysis of changes in the expression of ABCB1 and its methylation, taking into account their potential associations with the clinicopathological parameters of LUAD and LUSC. The TNMplot, UALCAN, cBioPortal, PrognoScan, and MEXPRESS databases were used to investigate the role of this gene in lung cancer progression. ABCB1 expression in lung tissue was significantly downregulated in cancer cells, but differences also resulted from age, gender, ethnicity, and smoking cessation. Moreover, decreased levels of gene transcript were associated with both a higher stage of cancer and a lower probability of survival. It is worth emphasizing that the presence/direction of ABCB1 expression changes are frequently unique to specific histological tumor subtypes. Finally, it is equally important that the main methylation promoter is one of the causes of decreased gene expression in lung cancer cells. Taken together, these data establish the ABCB1 transporter gene as an important prognostic factor that could alter disease progression and contribute to the survival of cancer patients.