Presence Of Mucinous Component Research Articles

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer-A Multicentre Propensity-Score-Matched Retrospective Analysis.

KRASG12C-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. A multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/- bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment-effect interactions. KRASG12D-mutated patients were analysed as control. One hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. However, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. No difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). First-line irinotecan-based regimens provided better survival results in KRASG12C-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations.

Effect of microsatellite instability on histopathological parameters and prognosis in colon cancers

Purpose: The aim of this study was to compare the clinicopathological features, while evaluating the frequency of MSI, and the survival rates in these patients in our patient group with MSI and microsatellite stabil (MSS) colorectal carcinomas (CRCs).Materials and Methods: We retrospectively enrolled 146 patients who underwent colon resection between the years of 2014-2022. The expression of MSI status was evaluated by immunohistochemistry. The association of MSI status, presense of tumor-infiltrating lymphocytes (TILs), and tumor budding score with a patient’s survival was assessed by the Kaplan–Meier method and Cox regression analysis.Results: There were 104 (71.2%) MSS cases and, 42 (28.8%) MSI cases. 15 (10.3%) MSI tumors were found to be MSI-low, and 27 (18.5%) to be MSI-high. MSI tumors were significantly associated with younger patients (<50), earlier stage (T1-T2), right localization, lower rate of lymph node metastasis, presence of mucinous component and TILs response. The Cox-regression model revealed TILs, tumor budding score, and MSI are variables that significantly affect survival. The presence of TILs exhibited a protective effect (Hazard ratio (HR)=0.446), which decreased the mortality risk by 2.24 times for the follow-up period, while the presence of high TBS increased the risk of mortality by HR=3.22.Conclusion: This study revealed that patients with MSI CRCs may show unique clinicopathological features and should be evaluated using some guiding parameters that will improve survival.

KRAS/NRAS Mutational Analysis and Clinicopathologic Correlation of Colorectal Carcinoma: A Single Institute Experience From Turkey

Background: Colorectal carcinoma (CRC) is the second most frequent cause of cancer-related death for both sexes. Clinical and pathological correlates of Kirsten rat sarcoma viral oncogene/neuroblastoma ras viral oncogene (KRAS/NRAS) mutant tumors are important for therapy response, especially in metastatic CRCs. The aim of this study is to determine the frequency of KRAS/NRAS mutations and investigate the clinicopathologic characteristics of KRAS/NRAS mutant and rat sarcoma (RAS)-wild type CRCs. Methods: Pathology archives were searched for CRCs between 2014 and 2015, retrospectively. We reevaluated tumor slides for Crohn-like infiltrate, tumor infiltrating lymphocytes, tumor budding, presence of mucinous component, and signet-ring cell morphology. Tumor grade, depth of invasion, lymph node metastases, distant metastases, lymphovascular and perineural invasion, polyp type, and DNA mismatch repair status were derived from their pathology reports. Formalin-fixed, paraffin-embedded tissues were examined for KRAS/NRAS mutation status. Mutation status and their clinicopathologic correlates were evaluated. Results: KRAS and NRAS mutations were detected in 43.6% and 10% of the CRCs, respectively. KRAS mutations were associated with multiple organ metastasis and CRCs with solid growth pattern did not harbor RAS mutations. Well differentiated CRCs were more common in NRAS mutant and RAS-wild type CRCs in comparison to RAS mutant tumors. NRAS mutant CRCs were more frequent in the left colon and rectum. Conclusion: In this study, we identified that KRAS mutations were associated with multiple organ metastasis and CRCs with solid growth pattern did not harbor RAS mutations. Also, NRAS mutant tumors were more common in the left colon and rectum concordant with the previous studies. Keywords: colorectal carcinoma, metastatic colorectal carcinoma, KRAS, NRAS

Abstract 5594: Inmune gene expression by nCounter in mucinous adenocarcinoma lung cancer

Abstract Introduction: Although immune checkpoint inhibitors have become a standard of care for multiple cancer types; currently used biomarkers, such as PD-L1 expression, MSI or TMB, fail to identify all responders. In addition, little is known about markers of response to immunotherapy in some infrequent histological subtypes, such as mucinous adenocarcinoma of the lung. Gene expression signatures incorporating not only PD-L1 but also other immune modulators can have a better predictive power, particularly in these histological subtypes. Methods: A cohort of 165 baseline samples from with stage I-IV non-small cell lung cancer (NSCLC) patients was retrospectively analyzed, 55 stage I-IIIA mucinous adenocarcinomas (MA), 31 stage I-IIIA nonmucinous adenocarcinomas (NMA) and 79 stage IIIB-IV NMAs. RNA was extracted from FFPE tumor samples and the expression levels of a 7-gene immune signature (CD4, CD8A, FOXP3, GZMM, INFG, CD274 and PDCD1) were determined using a nCounter panel. Krustal-Wallis test was used for statistical comparisons. Results: No significant differences were observed in the expression levels of FOXP3 and PDCD1 (codifying forkhead box P3 and PD-1) between the three groups analyzed. In contrast, GZMM, IFNG and CD4 expression (codifying granzyme M, interferon gamma and CD4) was significantly higher in early stage MA compared to stage I-IIIA or stage IIIB-IV NMA. CD8A expression was significantly higher in early stage tumors, independently of the presence of mucinous component. In addition, the levels of CD274 mRNA (codifying PD-L1) were significantly higher in early stage MA compared to advanced stage NMA. Finally, among the stage I-IIIA MA, 27/55 (49%) were KRAS-mutant, but they did not show significant differences with KRAS-wt MAs in the expression of any of the genes tested. Conclusions: Mucinous adenocarcinoma of the lung shows a different pattern of expression of immune-related genes, which may influence response to immunotherapy. Citation Format: Ruth Román Lladó, Cristina Aguado Esteban, Ana Giménez-Capitán, Ueda Daisuke, Masaoki Ito, Yasuhiro Tsutani, Yoshihiro Miyata, Cristina Teixidó, Noemí Reguart, Morihito Okada, Sonia Rodríguez, Ariadna Balada, Erika Aldeguer, Santiago Viteri Ramirez, Maria Gonzalez Cao, Andrés Aguilar, Rafael Rosell, Miguel Angel Molina Vila. Inmune gene expression by nCounter in mucinous adenocarcinoma lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5594.

Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression

Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with β-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.

Abstract 783: High microsatellite instability predicts good prognosis in intestinal type gastric cancers

Abstract A subset of gastric cancers shows high microsatellite instability (MSI-H). The reported clinicopathologic features of MSI-H gastric cancers are heterogeneous, and specific factors associated with prognosis have not been identified. We analyzed the clinicopathologic characteristics and prognostic factors in a large series (161 cases) of MSI-H gastric cancers, and compared the results to 315 cases of microsatellite stable or low MSI gastric cancers. The frequency of MSI-H gastric cancers was 9.0% (161/1786). MSI-H gastric cancers have distinct clinicopathologic features including female gender, older age, antral location, protruded gross type (Borrmann typeIand type II), well to moderate differentiation, intestinal type of Lauren classification, expanding type of Ming classification, non signet ring cell component, presence of mucinous component, moderate to severe lymphoid stromal reaction, and lower tumor stage. The MSI-H phenotype was associated with better prognosis (P = .044), and male gender (P = .035, HR: 0.23), intestinal/mixed type of Lauren classification (P <.001, HR: 0.09) and lower tumor stage (1 and 2) (P = .001, HR: 0.08) were independently favorable prognostic factors. With unique clinicopathologic features, the intestinal type MSI-H gastric cancers are associated with good prognosis and can be classified as a different subset of gastric cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 783.

Peritumoral Inflammatory Infiltrate is not a Prognostic Factor in Distal Rectal Cancer Following Neoadjuvant Chemoradiation Therapy

BackgroundPeritumoral inflammatory response has been considered a good prognostic factor for colorectal cancer. However, this has not been evaluated in patients submitted to neoadjuvant therapy for distal rectal cancer. For this reason, we decided to study the effect of the presence of this pathological finding on disease recurrence and survival. MethodsThe peritumoral inflammatory infiltrate from recovered pathological specimens of patients operated after neoadjuvant therapy for distal rectal cancer was graded (positive or negative). Patients were compared according to the presence of peritumoral inflammatory response. ResultsOf the 168 patients, 63 (37%) patients had a peritumoral inflammatory response. The lack of peritumoral inflammatory response was significantly associated with the presence of mucinous component (13 vs 3%; p = 0.02). Five-year overall survival (91 vs 81%) and disease-free survival (57 vs 48%) were not significantly different between patients with and without peritumoral inflammatory response (p = 0.5 and 0.3, respectively). ConclusionsPeritumoral inflammatory response is not a favorable prognostic factor in patients with distal rectal cancer after neoadjuvant chemoradiation therapy. Possibly, the immunosuppressive action of chemoradiation therapy may lead to a loss of function of the immunological response, which may represent a disadvantage of the neoadjuvant approach for the management of distal rectal cancer.