Mucinous Subtype Research Articles

ID: 3521525 DIAGNOSTIC ACCURACY OF INTRACYSTIC CONCENTRATIONS OF GLUCOSE AND CEA IN IDENTIFYING MUCIN PRODUCING CYSTIC NEOPLASMS OF THE PANCREAS: A MULTICENTER RETROSPECTIVE COHORT STUDY OF HISTOLOGICALLY-PROVEN CYSTS

Pancreatic cystic lesions (PCLs) are encountered incidentally in 2.4-19.6% of the general population and the mucinous subtypes carry malignant potential. Differentiating mucinous from non-mucinous PCLs can present a diagnostic challenge. Current guidelines recommend the use of cyst fluid carcinoembryonic antigen (CEA) to identify mucinous PCLs, however its sensitivity and specificity can vary widely. Through the needle biopsy or DNA mutational analysis have yielded favorable results but clinical applicability is limited by cost and inaccessibility. Intracystic glucose has shown promise in differentiating mucinous PCLs, but data are limited to frozen specimens and PCLs without uniform histologic diagnostic confirmation. The aim of this study was to assess the diagnostic accuracy of intracystic glucose in differentiating mucinous from non-mucinous PCLs from fresh fluid of PCLs with confirmatory histologic diagnoses.

English

BACKGROUND Surface epithelial ovarian tumour (SEOT) develops from the outer surface of ovary. It accounts for more than 90 % of all the ovarian tumours. Most of the SEOT are benign. Few SEOT are of low malignant potential or high malignant potential. The purpose of this study was to assess the rate of expression of proliferative marker Ki-67 and staining pattern of p53 in various histological types of SEOT. METHODS It was a randomised type of study carried out in the Department of Pathology, GSVM Medical College, Kanpur, for 2 years. It included 100 random patients with surgically resected specimens of SEOT. Ki-67 immunohistochemistry (IHC) was performed on all malignant cases and few random benign cases; and the percentage of immunopositive cells in each case was expressed as Ki-67 labelling index (Ki-67 LI). p53 expression was interpreted as positive when cells showed diffuse and intense nuclear staining in malignant cases. RESULTS Out of 100 cases, 70 were benign and 30 were malignant. Cases comprised of serous and mucinous histological subtypes. In all malignant cases, Ki-67 expression was found to be positive (Ki-67 LI > 1 %). Highest Ki-67 LI of 52 % was associated with high grade serous cystadenocarcinoma. High grade serous carcinoma (HGSC) had higher p53 positivity. 88.8 % of HGSC were p53 positive. CONCLUSIONS Ki-67 is a cost-effective proliferative marker; therefore, its assessment can be included in routine histopathological report of SEOT for better understanding of the biologic behaviour and aggressiveness of the tumour. p53 expression was more common in HGSC and can help in discriminating between HGSC and lowgrade serous carcinoma (LGSC). KEYWORDS p53, Ki-67, Ovarian Tumour, Serous, Mucinous, SEOT

Brenner Borderline Ovarian Tumor: A Case Series and Literature Review.

Most frequent borderline ovarian tumors are serous and mucinous subtypes. Less frequent borderline diseases are endometrioid, clear-cell, and Brenner tumors (BBOT). Very little is known about the latter subtype, and most studies include very short series or case reports. The aim of this study is to determine the prognosis of a continuous series of BBOT and analyze data published in the literature on this rare entity. A retrospective review of patients with BBOT treated or referred to our institutions was conducted. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion. Overall, 17 patients were identified. Median age was 62 (range 42-85) years. Six patients underwent unilateral salpingo-oophorectomy, and 11 bilateral salpingo-oophorectomy +/- hysterectomy and/or staging surgery. In total, 16 patients had unilateral tumor, and all patients had stage I disease. Stromal microinvasion was observed in three cases. Median follow-up was 60 months (range 7-118 months). One patient developed a recurrence in contralateral ovary after unilateral salpingo-oophorectomy. One patient had previous history of urothelial tumor. Peritoneal staging surgery is not required because all patients reported had stage I disease. One recurrence occurred. When reviewing all the 82 cases reported in the literature (including ours), 9% had previous history or synchronous urothelial tumor, suggesting the need to carefully check for urological disease in patients with BBOT.

The impact of lymph node dissection on apparent Stage I epithelial ovarian carcinoma: A population-based study.

To explore the impact of lymphadenectomy on the prognosis of women of reproductive age with clinically apparent Stage I epithelial ovarian cancer (EOC). Data of women of reproductive age with Stage I EOC, diagnosed between 2010 and 2016, were extracted from the Surveillance, Epidemiology, and End Results database. Five-year cancer-specific survival (CSS) was evaluated using the Kaplan-Meier method. Multivariate Cox analysis was performed to evaluate the effect of lymph node dissection on survival. Propensity score (PS) matching was conducted to balance various clinicopathologic factors. Of 2222 patients included, 1609 (72.4%) received lymph node dissection. The rate of histopathologically confirmed lymph node metastasis was highest in serous subtype (10.2%) and lowest in mucinous subtype (2.2%). No significant difference between the lymphadenectomy and non-lymphadenectomy groups in 5-year CSS was observed in the original cohort (P=0.364) or in the PS matching cohort (P=0.248). Nevertheless, there was a significant difference between the lymphadenectomy and non-lymphadenectomy groups for patients with Stage IC EOC (92.4% vs. 88.1%, P=0.027). According to the multivariate analysis, performance of the lymphadenectomy was not significantly associated with CSS in the original cohort (P=0.163) or the PS matching cohort (P=0.101). Dissection of lymph nodes was not significantly associated with improved prognosis for most Stage I EOC, but, lymphadenectomy may be necessary for women of reproductive age with Stage IC subtype.

Histopathological analysis of mucinous breast cancer subtypes and comparison with invasive carcinoma of no special type

Mucinous breast cancer (MBC) is a rare histological type of breast cancer characterized primarily by mucin's production and extracellular presence. MBC is usually associated with a better prognosis than other invasive breast neoplasms. Because of the low prevalence, MBC biology is not well understood. The aim of the present study was to introduce the last 2-year experience regarding MBC pathological diagnostics in our clinical center and comparison of the obtained data with invasive breast carcinoma of no special type (NST) comprising the most common invasive breast cancer. We identified 24 MBC cases representing 3.09% of all 766 invasive breast cancers, including 15 cases of pure type and 9 mixed MBCs. The median MBC patients' age at presentation was 65.5 years. Compared to NST, MBC presented a higher T stage with a statistically larger tumor median size, although lower regional lymph node involvement, tumor histological grade and TNM stage. MBC is a rare type of breast cancer, accounting for about 4% of all diagnosed breast cancers. Our findings are consistent with those published in recent years and show significant differences between MBC and NST cancer patients and also highlight differences between pure and mixed MBC, emphasizing the essence of their differentiation. MBC is associated with a better long-term prognosis than NST and is characterized by the less aggressive biological behavior expressed through favorable clinicopathologic features in terms of tumor grade, regional lymph node involvement and hormone receptor status.

Rectal MRI after neoadjuvant chemoradiation therapy: a pictorial guide to interpretation.

Magnetic resonance imaging (MRI) is the current reference standard imaging modality for restaging rectal cancer after neoadjuvant chemoradiation and is used to guide clinical management decisions. This pictorial essay provides an illustrative atlas of the key MRI features used to assess rectal cancer after treatment. MRI findings of residual tumor including non-mucinous, mucinous, and signet-ring cell adenocarcinoma subtypes are correlated with histopathology. Imaging appearances of treatment changes that mimic residual tumor in the setting of confirmed pathological complete response at resection are illustrated. Treatment complications are also shown. Knowledge of these imaging findings and their importance may help radiologists comply with all elements of the structured reporting templates proposed by the Rectal Cancer Disease Focused Panel of the Society of Abdominal Radiology and by the European Society of Gastrointestinal and Abdominal Radiology.

Transcription Strikes Back: Clinical Utility of Lung Adenocarcinoma Subtypes.

Using transcriptional profiling, three robust subtypes of nonsquamous non-small cell lung cancer were defined, independently of initiating oncogenic driver events. Subtype-specific differential sensitivity to MEK1/2 inhibitors was reported and an interaction between the mucinous subtype, STK11/LKB1 genomic alterations, and inferior clinical outcomes with atezolizumab in the OAK clinical trial was identified.See related article by Daemen et al., p. 1162.

Abstract PD9-09: High tumor mutational burden (>=10 mut/Mb) is enriched in specific breast cancer pathological subtypes

Abstract Background: Pembrolizumab recently received pan-tumor FDA approval for the treatment of patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) >10 mutations per megabase (mut/Mb) and who have no satisfactory alternative treatment options. The KEYNOTE-119 and TAPUR trials have validated TMB as a predictive biomarker using TMB cutoffs of ≥ 10 mut/Mb and 9 mut/Mb, respectively, for benefit from single-agent pembrolizumab in subsets of patients with clinically advanced breast cancer (aBC). Limited data exist on which pathological subtypes of aBC are most likely to be TMB >10 mut/Mb (TMB-High). This study analyzed the frequency of TMB-High tumors in aBC subtypes to evaluate variations between subtypes and correlation with additional immunotherapy biomarkers. Methods: Utilizing the Foundation Medicine breast cancer database, 5,475 samples with aBC and pathological subtype information were identified. Pathological subtypes included in this study were ER+/HER2-negative invasive ductal carcinoma (IDC), ER-negative/HER2+ IDC (HER2+), triple negative IDC (TNBC), invasive lobular, inflammatory, metaplastic, mucinous and papillary. TMB was determined on 0.8-1.1 Mb of sequenced DNA, and microsatellite instability (MSI) was assessed across 114 loci in 564 cases. PD-L1 was determined in a subset of cases by immunohistochemistry (Ventana SP142). Results: TMB-High (>10 mut/Mb) was common in all breast cancer pathological subtypes except papillary carcinoma (Table 1). TMB-High was most often found in lobular, inflammatory and HER2+ carcinomas (16%, 14% and 12% of cases, respectively). Metaplastic, mucinous and papillary subtypes were least likely to be TMB-High (7%, 7% and 0% of cases, respectively). TMB-High was more common than MSI-High in all subtypes, excluding papillary. Emerging biomarkers that may play a role in mitigating immunotherapy response, such as MDM2 amplifications and STK11 alterations, were observed in most subtypes. The frequencies of these alterations, as well as alterations associated with FDA-approved therapies in breast cancer, are provided in Table 1 and will be further discussed. Conclusions: TMB-High (>10 mut/Mb) is common in most pathological subtypes of clinically advanced breast cancer and can identify patients not identified by MSI or PD-L1 testing who may benefit from immunotherapy. Based on the high percentage of advanced breast cancer patients who are TMB-High or have genomic alterations in other biomarkers associated with FDA-approved targeted therapies, comprehensive genomic profiling including TMB and MSI should be considered for all pathological subtypes. Table 1Pathological subtypeInvasive ductal carcinoma (IDC)ER+, HER2-negativeER-negative, HER2+Triple-negative (TNBC)Invasive Lobular CarcinomaInflammatory MetaplasticMucinousPapillaryCases (n)1,2371,9536411,180353892911Age55 (23-89)55 (20-89)53 (20-85)62 (24-89)54 (28-87)59 (28-89)55 (30-80)61 (38-78)Tumor mutational burden (TMB)TMB > 10 mut/Mb8%12%9%16%14%7%7%0%TMB > 20 mut/Mb2%2%3%7%6%2%3%0%Additional immunotherapy biomarkersMSI-High0.2%0.1%0.4%0%0%0%0%0%PD-L1+ (>1% Ventana SP142)N/AN/A47%N/AN/A26%0%N/AMDM2 amplification6%5%3%2%0%2%3%18%STK11 alteration1%1%2%1%3%3%3%0%Additional biomarkers associated with FDA-approved therapiesBRCA1/2 alteration3%/6%2%/3%7%/3%1%/4%6%/6%4%/3%3%/0%0%/9%ERBB2 amplification0%100%0%3%26%3%34%9%NTRK 1/2/3 rearrangement0%/0%/0%0%/0%/0%0%/0%/0%1%/0%/0%0%/0%/0%0%/0%/1%0%/0%/0%0%/0%/0%PIK3CA alteration38%38%19%56%34%38%21%36% Citation Format: Mason A Israel, Marni Tierno, Richard SP Huang, Kimberly McGregor, Ethan S Sokol, Prasanth Reddy, Jeffrey S Ross. High tumor mutational burden (>=10 mut/Mb) is enriched in specific breast cancer pathological subtypes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-09.

Mucinous, endometrioid, and serous ovarian cancers with peritoneal dissemination are potent candidates for P-cadherin targeted therapy: a retrospective cohort study

BackgroundAberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancer patients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future.MethodsA total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancer patients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed.ResultsP-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01).ConclusionsMucinous, endometrioid, and serous ovarian cancer patients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.

Death of 43 Indonesian women with ovarian cancer: A case series

BackgroundOvarian cancer is a gynecological cancer with a higher mortality than other gynecological cancers. Case reportThere were 43 cases of Indonesian women who died of ovarian cancer in 2015–2017. Patients were first diagnosed at the age of 40–59 years (65.11%), of which had normal BMI (62.72%) and mostly in stage III (39.53%). The histology was 88.3% epithelial ovarian cancer with the most subtypes of mucinous carcinoma (25.5%). The majority were referral patients (62.7%), but due to its malignancy, many died before receiving ovarian cancer treatment (40.74%). Of the 43 patients, 17 patients received chemotherapy, and 10 patients received a combination of surgical therapy and chemotherapy. Most of the deaths were caused by primary disease (69.77%). Patients with stages III and IV, as well as patients receiving surgery or chemotherapy alone had shorter survival times. ConclusionMost ovarian cancer patients are first diagnosed at stage III with the mucinous carcinoma subtype. Most deaths are caused by primary ovarian cancer. The therapy that provides the longest survival is a combination of surgery and chemotherapy.

Role of Retinoblastoma Protein Family (Rb/p105 and Rb2/p130) Expression in the Histopathological Classification of Borderline Ovarian Tumors.

Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. The identification of valuable markers for the diagnosis and classification of these tumors is in need. Among the molecular candidates, the Retinoblastoma (Rb) family members Rb/p105 and Rb2/p130 seem to play a pivotal role in ovarian cancer. In particular, Rb/p105, when in the unphosphorylated form, acts as a growth suppressor controlling cell cycle and tumor progression; whereas, the phosphorylated form activates gene transcription and cellular proliferation. While Rb/p105 is ubiquitously confined to the nuclei of cycling and quiescent cells, Rb2/p130 activity is also regulated by intracellular localization. According to this, Rb family members could represent a novel marker in diagnosis and classification risk for patients with BOT. In this study, we evaluated the expression and subcellular localization of proteins of the retinoblastoma (Rb) gene family in 65 ovarian borderline tumors. Statistically significant differences were found in nuclear and cytoplasmic expressions of Rb/p105 and Rb2/p130 according to different examined histotypes. In detail, the nuclear expression of Rb/p105 and Rb2/p130 was more frequently detected in serous (84.6%) than sero-mucinous (42.1%) and mucinous (50%) types. Conversely, the cytoplasmic expression of Rb2/p130 was not detected in serous tumors and frequently observed in mucinous subtypes (80%). Our findings suggest that Rb proteins do not play a key role in the tumor progression of serous borderline tumors since any cases showed cytoplasmic localization. By contrast, the observed higher cytoplasmic expression of Rb2/p130 in intestinal mucinous BOTs is indicative of Rb protein family involvement in the cancerogenesis pathway of mucinous ovarian tumors. Also, mucinous BOTs of intestinal-type, exhibiting low nuclear and high cytoplasmic levels of Rb2/p130 might potentially be considered a high-risk category of malignant evolution. Further studies on larger series are needed to clarify how BOTs could be stratified in different prognostic groups according to their Rb proteins immunohistochemical profile.

Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database.

Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). We retrospectively collected data of surgically resected stage I and II adenocarcinoma. anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. Materials and method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.

Modeling the Diversity of Epithelial Ovarian Cancer through Ten Novel Well Characterized Cell Lines Covering Multiple Subtypes of the Disease.

Cancer cell lines are amongst the most important pre-clinical models. In the context of epithelial ovarian cancer, a highly heterogeneous disease with diverse subtypes, it is paramount to study a wide panel of models in order to draw a representative picture of the disease. As this lethal gynaecological malignancy has seen little improvement in overall survival in the last decade, it is all the more pressing to support future research with robust and diverse study models. Here, we describe ten novel spontaneously immortalized patient-derived ovarian cancer cell lines, detailing their respective mutational profiles and gene/biomarker expression patterns, as well as their in vitro and in vivo growth characteristics. Eight of the cell lines were classified as high-grade serous, while two were determined to be of the rarer mucinous and clear cell subtypes, respectively. Each of the ten cell lines presents a panel of characteristics reflective of diverse clinically relevant phenomena, including chemotherapeutic resistance, metastatic potential, and subtype-associated mutations and gene/protein expression profiles. Importantly, four cell lines formed subcutaneous tumors in mice, a key characteristic for pre-clinical drug testing. Our work thus contributes significantly to the available models for the study of ovarian cancer, supplying additional tools to better understand this complex disease.

Identification and validation of differential plasma proteins levels in epithelial ovarian cancer

Diagnosis of Ovarian cancer (OC) has been a challenge, the purpose, therefore is to identify plasma proteins differentially expressed in epithelial ovarian cancer patients. Human plasma samples from patients with OC (n = 138), benign tumors (n = 20) and controls (n = 238) were used. Tandem Mass Tag (TMT) based quantitative analysis by high resolution mass spectrometry, was followed by validation using Quantibody array and ELISA techniques. 507 plasma proteins showed differential protein levels in OC plasma samples. 21 proteins were validated using Quantibody array. Further, nine proteins (CA125, CFD, CST3, ICAM1, IGFBP2, IGFBP3, SPP1, TSP1 and VEGFA) which showed significant differences in protein levels in Quantibody array analysis were validated using ELISA. In ELISA, the levels of CA125, IGFBP2, ICAM1 and SPP1 were significantly increased and levels of Adipsin and TSP1 were decreased in tumors compared to controls and benign group. Epithelial ovarian cancer diagnosis model combining five markers (CA125, IGFBP2, SPP1, TSP1 and ADI) showed 90.24% sensitivity and 94.87% specificity. In conclusion a panel of 5 plasma proteins has been found to be useful in distinguishing plasma samples from epithelial ovarian cancers from patients with benign tumors and healthy normal subjects. This has the potential as a diagnostic assay for epithelial ovarian cancer. SignificanceThe significance of this case-control study is based on the large and well defined ovarian cancer patient population (epithelial ovarian cancers including serous and mucinous subtypes), age matched controls and benign ovarian tumors. This study incorporates a discovery phase involving quantitative proteomic analysis of immune-depleted plasma followed by two levels of validation studies involving a selected list of proteins using antibody arrays and ELISA. The validations were performed on an independent set of samples comprising of epithelial ovarian cancer subtypes, controls and benign tumors. The multiple marker combination comprising of Adipsin, CA125, IGFBP2, SPP1 and TSP1 identified in the study by ELISA could enable rapid translation to a larger screening study.

Cytoplasmic VDR expression as an independent risk factor for ovarian cancer

The vitamin D receptor (VDR), primarily known as a crucial mediator of calcium homeostasis and metabolism, has been shown to play a significant role in various cancer entities. Previous studies have focused on vitamin D and its receptor in gynecological cancers, noting that the receptor is upregulated in epithelial ovarian cancer (EOC). The aim of this study is to analyze the prognostic impact of VDR and its functional significance in ovarian cancer. Through immunohistochemistry, VDR staining was examined in 156 ovarian cancer samples. Evaluation of VDR staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score, and the scores were classified into high- and low-level expressions. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. Differences in cytoplasmic VDR expression were identified between the histological subtypes (p = 0.001). Serous, clear cell, and endometrioid subtypes showed the highest staining, while the mucinous subtype showed the lowest. Cytoplasmic VDR correlated with higher FIGO stage (p = 0.013; Cc = 0.203), positive lymph node status (p = 0.023; Cc = 0.236), high-grade serous histology (p = 0.000; Cc = 0.298) and grading from the distinct histological subtypes (p = 0.006; Cc = − 0.225). Nuclear VDR did not correlate with clinicopathological data. High cytoplasmic expression of VDR was associated with impaired overall survival (HR 2.218, 32.5 months vs. median not reached; p < 0.001) and was confirmed as a statistically independent prognostic factor in the Cox regression multivariate analysis. Additional knowledge of VDR as a biomarker and its interactions within the mitogen-activated protein kinase (MAPK) signaling pathway could potentially improve the prognosis of therapeutic approaches for specific subgroups in EOC.

Mutational profiles of lung adenocarcinoma subtypes.

e21517 Background: Genomic profiling of lung adenocarcinoma has been studied, however, different histological subtypes were not carefully distinguished, especially in patients with mixed subtypes. Methods: Fifty-three invasive adenocarcinoma (IA) FFPE samples from lung cancer patients with detailed histological classifications were panel sequenced and analyzed. Results: Among the 53 IAs, acinar (n = 42), lepidic (n = 34) and papillary (n = 25) were most dominant subtypes and were frequently mixed with other types. Zero to 14 mutations were identified in each sample (median = 4). Thirteen of the 42 (31%) tumors containing acinar subtype harbored TP53 mutations, while none of the 11 (0%) acinar negative tumors harbor TP53 mutation; six of the 42 (14.3%) acinar positive had RBM10 mutations, while 5 of the 11 (45.4%) acinar negative had RBM10 mutations. Three of the 34 (8.8%) tumors with lepidic subtypes harbored TP53 mutations, while 10 of the 19 (52.6%) lepidic negative tumors harbored TP53 mutations; Ten of 34 (29.4%) lepidic positive tumors harbored RBM10 mutations, while 1 of the 19 (5.3%) lepidic negative tumors harbored RBM10 mutations. All papillary tumors were mixed with other subtypes. Conclusions: Different histological subtypes have different mutational features. Acinar subtypes harbor more TP53 and less RBM10 mutations than acinar negative tumors; lepidic subtypes harbor less TP53 and more RBM10 mutations than lepidic negative tumors. Lack of mucinous, micropapillary and solid subtypes requires further study to analyze their mutational signatures.

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer.

To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%-83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.

Lymphovascular Infiltration, Not Depth of Invasion, is the Critical Risk Factor of Metastases in Early Colorectal Cancer: Retrospective Population-based Cohort Study on Prospectively Collected Data, Including Validation.

To identify clinical and histopathological risk factors of LNM in T1 CRC. The requisite of additional surgery after locally resected T1 CRC is dependent on the risk of LNM. Depth of submucosal invasion is used as a key predictor of lymphatic metastases although data are conflicting on its actual impact. Retrospective population-based cohort study on prospectively collected data on all patients with T1 CRC undergoing surgical resection in Sweden, 2009-2017 and Denmark 2016-2018. The Danish cohort was used for validation. Potential risk factors of LNM investigated were; age, sex, tumor location, submucosal invasion, grade of differentiation, mucinous subtype, lymphovascular, and perineural invasion. One hundred fifty out of the 1439 included patients (10%) had LNM. LVI (P < 0.001), perineural invasion (P < 0.001), mucinous subtype (P = 0.006), and age <60 years (P < 0.001) were identified as independent risk factors whereas deep submucosal invasion was only a dependent (P = 0.025) risk factor and not significant in multivariate analysis (P = 0.075). The incidence of LNM was 51/882 (6%) in absence of the independent risk factors. The Danish validation cohort, confirmed our findings regarding the role of submucosal invasion, LVI, and age. This is a large study on LNM in T1 CRC, including validation, showing that LVI and perineural invasion, mucinous subtype, and low age constitute independent risk factors, whereas depth of submucosal invasion is not an independent risk factor of LNM. Thus, our findings provide a useful basis for management of patients after local excision of early CRC.

Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Barretos Cancer Hospital.

Background: Colorectal cancer (CRC) is the third most frequent and the second deadliest cancer worldwide. The ethnic structure of the population has been gaining prominence as a cancer player. The purpose of this study was to determine the genetic ancestry of Brazilian CRC patients. Moreover, we intended to interrogate its impact on patients' clinicopathological features.Methods: Retrospective observational cohort study with 1,002 patients with CRC admitted from 2000 to 2014 at Barretos Cancer Hospital. Following tumor DNA isolation, genetic ancestry was assessed using a specific panel of 46 ancestry informative markers. Survival rates were obtained by the Kaplan–Meier method, and the log-rank test was used to compare the survival curves. Multivariable Cox proportional regression models were used to estimate hazard ratios (HRs).Results: We observed considerable admixture in the genetic composition, with the following average proportions: European 74.2%, African 12.7%, Asian 6.5%, and Amerindian 6.6%. The multivariate analysis for cancer-specific survival showed that clinical stage, lymphovascular invasion, and the presence of recurrence were associated with an increased relative risk of death from cancer (p < 0.05). High African proportion was associated with younger age at diagnosis, while high Amerindian proportion was associated with the mucinous histological subtype.Conclusions: This represents the larger assessment of genetic ancestry in a population of Brazilian patients with CRC. Brazilian CRC patients exhibited similar clinicopathological features as described in Western countries.Impact: Genetic ancestry components corroborated the significant admixture, and importantly, patients with high African proportion develop cancer at a younger age.