Cases Of Colorectal Adenocarcinoma Research Articles

Keratin 6A Is Expressed at the Invasive Front and Enhances the Progression of Colorectal Cancer

Keratins (KRTs) are intermediate filament proteins in epithelial cells, and they are important for cytoskeletal organization. KRT6A, classified as a type II KRT, is normally expressed in stratified squamous epithelium and squamous cell carcinomas. Little is known about the expression and role of KRT6A in adenocarcinomas. We investigated the clinicopathologic and molecular biological significance of KRT6A in colorectal adenocarcinoma. Immunostaining of colorectal adenocarcinoma cases treated at our institution demonstrated that KRT6A showed significantly stronger expression at the invasive front than that at the tumor center (P < .0001). The high KRT6A–expression cases (n = 47) tended to have a high budding grade associated with significantly worse prognoses. A multivariate analysis revealed that the KRT6A expression status was an independent prognostic factor for overall survival (P = .0004), disease-specific survival (P = .0097), and progression-free survival (P = .0033). The correlation between KRT6A and patient prognoses was also validated in an external cohort from a published data set. To determine the function of KRT6A in vitro, KRT6A was overexpressed in 3 colon cancer cell lines: DLD-1, SW620, and HCT 116. KRT6A overexpression increased migration and invasion in DLD-1 but did not in SW620 and HCT116. In 3-dimensional sphere-forming culture, KRT6A expression enhanced the irregular protrusion around the spheroid in DLD-1. Our findings in this study indicated that KRT6A expression is a valuable prognostic marker of colorectal cancer and KRT6A may be involved the molecular mechanism in the progression of invasive areas of colorectal cancer.

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma.

The tumor protein 53 (TP53) tumor suppressor protein (17p13.1) acts as a significant regulator for the cell cycle normal function. The gene is frequently mutated in colorectal adenocarcinoma (CRC) patients and is associated to poor prognosis and low response rates to chemo-targeted therapy. Our purpose was to correlate TP53 expression with Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3) and a major negative regulator in the TP53-MDM2 auto-regulatory pathway. A total of forty (n=40) colorectal adenocarcinoma (CRC) cases were included in this study. An immunohistochemistry-based assay was implemented by using anti-TP53 and anti-MDM2 antibodies in the corresponding tissue sections. Additionally, a digital image analysis assay was implemented for objectively measuring TP53/MDM2 immunostaining intensity levels. TP53 protein overexpression was detected in 27/40 (67.5%), whereas MDM2 overexpression in 28/40 (70%) cases. Interestingly, in 21/40 (52.5%) cases, a combined TP53/MDM2 co-expression was detected, whereas in 6/40 (15%), a combined loss of expression was identified (overall co-expression: p=0.119). p53 overexpression was significantly correlated to grade of the examined cases (p=0.001), whereas MDM2 to stage and max diameter of the malignancies (p=0.001 and 0.024, respectively). TP53/MDM2 over expression is a frequent and significant genetic event in CRCs associated with an aggressive biological behavior, as a result of increased dedifferentiation grade and advanced stage/elevated tumor volume, respectively. MDM2 oncogene overactivation combined with mutated and overexpressed TP53 is observed in sub-groups of patients leading to specific gene/protein signatures - targets for personalized chemotherapeutic approaches.

Incidence, Severity and Clinical Correlation of Oxaliplatin Induced Neuropathy in Patients with Colorectal Cancer: A Single Institutional Experience

Background: Colorectal cancer is the third most commonly diagnosed cancer worldwide, and its incidence is increasing in developing countries. Chemotherapy plays a significant role in the treatment of locally advanced and metastatic colorectal cancer. Oxaliplatin has remained the backbone of the treatment of colorectal carcinoma. The primary dose-limiting toxicity of oxaliplatin is neuropathy, which can reduce compliance during therapy and impair daily living activities. With limited data regarding the occurrence of oxaliplatin-induced peripheral neuropathy (OIPN) in the Indian population, we aimed to determine the incidence and severity of oxaliplatin-induced neurotoxicity and its clinical correlation with various clinical parameters in patients with colorectal carcinoma in a cancer care centre from North-East India. Material and Methods: A prospective observational analysis was performed on all histologically confirmed cases of colorectal adenocarcinoma who received oxaliplatin-based chemotherapy either in an adjuvant setting or first-line palliative setting at Dr. B. Borooah Cancer Institute between April 2019 to March 2020. Results: Our study evaluated 76 patients with colorectal carcinoma with a mean age of 54.07 ± 10 years. The majority (65.8%) of the patients had adenocarcinoma of the colon, and 34.2% had rectal adenocarcinoma. Twenty-three (30.3%) patients presented with metastatic disease. Oxaliplatin-based chemotherapy regimens were either CAPOX (72.4%) or FOLFOX (27.6%). Acute OIPN was observed in 59 patients (77.6%), and the most common symptom was cold-induced perioral paraesthesia. The most frequent grade for acute OIPN was grade II (30.3%). Chronic OIPN was seen in 47 (61.8%) patients, with the majority developing grade II neuropathy and was manifested mainly after 4th cycle of chemotherapy. The incidence of OIPN was higher in the patients aged ≥60 years, with a cumulative oxaliplatin dose of &gt; 1000 mg/m2 and baseline low serum magnesium or calcium level. Conclusion: Oxaliplatin is one of the essential chemotherapy drugs used in colorectal cancer with significant dose-limiting toxicity of peripheral neuropathy. Well-timed identification of neuropathic symptoms can increase treatment adherence and improve the patient’s quality of life.&#x0D;

Ring Finger 43 Hot-spot Frameshift Mutation G659V in Colorectal Cancer Patients: Report from a Tertiary Cancer Care Hospital in North India.

The Ring Finger 43 (RNF43) is a tumor suppressor gene that negatively regulates the Wnt/β-catenin signaling. The p.G659fs is a recurrent RNF43 C-terminal truncating variant frequent in colorectal cancer (CRC) patients. We aimed to identify this hotspot variant in CRC patients and assessed the relationship between the mutation, clinical characteristics, and tumor β-catenin localization. Formalin-fixed, paraffin-embedded tissue samples of upfront, surgically resected, sporadic colorectal adenocarcinoma cases were selected. The p.G659fs mutation was determined by capillary sequencing with sequence-specific primers. Tissue microarray and immunohistochemistry were employed to analyze nuclear β-catenin expression and the expression of mismatch repair (MMR) proteins, respectively. In addition, clinical details were retrieved from the hospital medical records and data were analyzed. The RNF43 p.G659fs mutation was observed in 8% of CRC patients. In total, 25% of tumors showed a loss of immunostaining for one or more MMR proteins and 14.6% of tumors showed positive nuclear β-catenin staining. The p.G659fs variant was significantly enriched in MMR-deficient tumors (P = 0.04). Importantly, no correlation was observed between the variant and nuclear β-catenin localization (P = 0.48), indicating a Wnt-independent role of this variant in CRC tumors. To the best of our knowledge, this is the first study from North India to show the involvement of RNF43 p.G659fs variant in CRC patients. The mutation correlated with MMR protein deficiency and seems to be conferring tumorigenicity independent of the Wnt pathway.

Clinicopathological Profile of Colorectal Adenocarcinoma in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak

Background: Colorectal adenocarcinoma is ranked third globally in the category of the most commonly diagnosed cancers, as reported by the Global Burden of Cancer (GLOBOCAN) survey in 2020. This condition ranks as the second leading cause of death from cancer with a mortality of 9.40%. Therefore, this study aimed to discover the clinicopathological profile of colorectal adenocarcinoma in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak in 2017–2020. Methods: This descriptive study used secondary data from the histopathology reports of the Anatomical Pathology Laboratory obtained by total sampling, which were processed using Microsoft Excel. Results: The total number of colorectal adenocarcinoma patients was 148, and the majority were in the category of 53–61 years, accounting for 30.41%, and 51.35% were female. The majority of the anatomical sites of tumors were in the “Rectum Not Otherwise Specified (NOS)”, with a percentage of 35.14%. The most frequent histopathological subtype was adenocarcinoma NOS, accounting for 85.81%, while the majority of differentiation grade was well differentiated, with a percentage of 90.54%. The most TNM (Tumor, Node, Metastatic) staging system of the American Joint Committee on Cancer (AJCC) was IIA (33.78%). Based on the classification using the Dukes staging system, the most stage suffered by patients was C2 with a percentage of 39.86%. Conclusions: In conclusion, the incidence of diagnosed colorectal adenocarcinoma cases increased yearly in the Anatomical Pathology Laboratory of Dr. Soedarso Hospital Pontianak. Further study of the clinical characteristics and analysis of risk factors in colorectal adenocarcinoma patients were important to support the development of effective preventive strategies.

Expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma.

To investigate the expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma and adjacent tissues. The expression of COX-2 and NUCB1 and their effects on prognosis were predicted using bioinformatics. Immunohistochemistry was used to identify the expression of two molecules in 56 cases of colorectal adenocarcinoma and the surrounding tissues. The expression of two molecules and their association with clinicopathological variables were examined using the chi-square test. The association between COX-2 and NUCB1 was investigated using the Spearman correlation test. The STRING database revealed that COX-2 and NUCB1 were strongly linked. According to the UALCAN and HPA database, COX-2 was upregulated while NUCB1 was downregulated in colorectal adenocarcinoma, both at the protein and gene levels. The OS times for COX-2 and NUCB1 high expression, however, exhibited the same patterns. The rate of positive COX-2 immunohistochemical staining in cancer tissues was 69.64% (39/56), which was significantly higher than the rate in healthy tissues 28.57% (16/56). NUCB1 was expressed positively in cancer tissues at a rate of 64.29% (36/56) compared to just 19.64% (11/56) in neighboring tissues. The positive expression levels of COX-2 and NUCB1 were both closely related to clinical stage, differentiation degree, and lymphatic metastases (P < 0.05). In colorectal cancer, COX-2 and NUCB1 expression were significantly correlated (rs = 0.6312, P < 0.001). Both COX-2 and NUCB1 are overexpressed and significantly associated in colorectal adenocarcinoma.

Racial/Ethnic Disparities in the Era of Minimally Invasive Surgery for Treatment of Colorectal Cancer.

Minimally invasive (laparoscopic and robotic) surgery (MIS) for colorectal cancer is associated with improved outcomes. We sought to characterize possible disparities in surgical approach and outcomes. In this cross-sectional study, colorectal adenocarcinoma cases among non-Hispanic white (NHW), non-Hispanic Black (NHB), and Hispanic patients were identified using the National Cancer Database (2010-2017). Logistic and Poisson regressions, generalized logit models, and Cox proportional hazards were used to assess outcomes, with reclassification of surgery type if converted to open. NHB patients were less likely to undergo robotic surgery. After multivariable analysis, NHB patients were 6% less likely, while Hispanic patients were 12% more likely to undergo a MIS approach. Lymph node retrieval was higher (> 1.3% more, p < 0.0001) and length of stay was shorter (> 17% shorter, p < 0.0001) for MIS approaches. Unplanned readmission was lower for MIS colon cancer operations compared with open operations, but not for rectal cancer. Race/ethnicity-adjusted risk of death was lower with MIS approaches for colon as well as rectal cancer. After adjusting for surgery type, risk of death was 12% lower for NHB and 35% lower for Hispanic patients compared with NHW patients. Hispanic patients had 21% lower risk of death, while NHB patients had 12% higher risk of death than NHW patients with rectal cancer, after adjusting for surgery type. Racial/ethnic disparities exist in utilization of MIS for colorectal cancer treatment, disproportionately affecting NHB patients. Since MIS has the potential to improve outcomes, suboptimal access may contribute to harmful and thus unacceptable disparities in survivorship.

Restaging MRI of Rectal Adenocarcinoma after Neoadjuvant Chemoradiotherapy: Imaging Findings and Potential Pitfalls

Rectal adenocarcinoma constitutes about one-third of all colorectal adenocarcinoma cases. Rectal MRI has become mandatory for evaluation of patients newly diagnosed with rectal cancer because it can help accurately stage the disease, impact the choice to give neoadjuvant therapy or proceed with up-front surgery, and even direct surgical dissection planes. Better understanding of neoadjuvant chemoradiotherapy effects on rectal tumors and recognition that up to 30% of patients can have a pathologic complete response have opened the door for the nonsurgical "watch-and-wait" management approach for rectal adenocarcinoma. Candidates for this organ-preserving approach should have no evidence of malignancy on all three components of response assessment after neoadjuvant therapy (ie, digital rectal examination, endoscopy, and rectal MRI). Hence, rectal MRI again has a major role in directing patient management and possibly sparing patients from unnecessary surgical morbidity. In this article, the authors discuss the indications for neoadjuvant therapy in management of patients with rectal adenocarcinoma, describe expected imaging appearances of rectal adenocarcinoma after completion of neoadjuvant therapy, and outline the MRI tumor regression grading system. Since pelvic sidewall lymph node dissection is associated with a high risk of permanent genitourinary dysfunction, it is performed for only selected patients who have radiologic evidence of sidewall lymph node involvement. Therefore, the authors review the relevant lymphatic compartments of the pelvis and describe lymph node criteria for determining locoregional nodal spread. Finally, the authors discuss limitations of rectal MRI, describe several potential interpretation pitfalls after neoadjuvant therapy, and emphasize how these pitfalls may be avoided. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia

Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a Uniform Manifold Approximation and Projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

Low MTUS1 Protein Expression Is Associated with Poor Survival in Patients with Colorectal Adenocarcinoma.

Microtubule-associated tumor suppressor 1 (MTUS1) is a novel tumor suppressor protein involved in cell proliferation, migration, and tumor growth. MTUS1 is thought to be downregulated in various human cancers and associated with poor prognosis. We evaluated the clinicopathologic significance and prognostic value of MTUS1 in colorectal adenocarcinoma. Immunohistochemical staining for MTUS1 was performed on tissue microarrays of 393 colorectal adenocarcinoma cases, and MTUS1 staining was classified into high- and low-expression groups. Then, we investigated the correlations between MTUS1 protein expression and various clinicopathological parameters and patient survival. MTUS1 protein was expressed at various grade levels in the cytoplasm of tumor cells, which showed loss or decreased expression of MTUS1. A total of 253 cases (64.4%) were classified into the low MTUS1 protein expression group and 140 cases (35.6%) into the high MTUS1 expression group. A low level of MTUS1 protein significantly correlated with tumor size (p = 0.047), histological grade (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.047), and lymph node metastasis (p < 0.001). Survival analyses showed that patients with low MTUS1 protein expression had worse overall survival (p = 0.007, log-rank test) and worse recurrence-free survival (p = 0.019, log-rank test) than those with high MTUS1 expression. Low MTUS1 protein expression is associated with adverse clinicopathological characteristics and poor survival outcomes in patients with colorectal adenocarcinoma. These results suggest that MTUS1 functions as a tumor suppressor in colorectal adenocarcinoma and could be a potential prognostic biomarker.

Association Between the Immunohistochemistry Expression of E-cadherin, Beta-Catenin, and CD44 in Colorectal Adenocarcinoma.

Background Colorectal cancer is a leading cause of cancer-related deaths worldwide, and epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. In EMT, there is downregulation of E-cadherin, an intracellular adhesion molecule, as well as mutations in beta-catenin genes. On immunohistochemistry (IHC), the expression of CD44 portrays stem cell differentiation, which, in turn, is strongly associated with EMT. Thus, newer targeted therapies can be advised based on the expression of EMT and stem cell differentiation. Aims and objectives To determine the IHC expression of E-cadherin, beta-catenin, and CD44 in colorectal adenocarcinoma and find the association of the IHC expression of E-cadherin, beta-catenin, and CD44 with the histopathological grade, stage, lymph node metastasis, and lymphovascular invasion of colorectal adenocarcinoma. Materials and methods Fifty histologically proven cases of colorectal adenocarcinoma from 2016 to 2021 were included in this study, and clinicopathological dataincluding age, gender, grading, TNM (tumour, node, and metastasis) staging, and lymph node metastasiswere collected and hematoxylin and eosin slides were reviewed. IHC staining for E-cadherin, beta-catenin, and CD44 was done for all cases using the peroxidase and anti-peroxidase method, and the results were analysed. Results Peak incidence occurred in the 61-70 years age group (36%), and the most common site of the tumour was the rectal area (48%). The majority of the cases were in TNM stage II (37.3%), and a low expression of E-cadherin was found to be associated with higher T stage (p = 0.03), TNM staging (p = 0.04), as well as the presence of lymph node metastasis (p = 0.006). High beta-catenin expression was observed to have a significant correlation with a higher T stage (p = 0.006) and TNM staging (p = 0.005), while high CD44 expression was found to be associated with lymph node metastasis (p = 0.01). Altered expression of EMT-related proteins (E-cadherin and beta-catenin) showed a significant correlation with higher T stage (p = 0.03), TNM staging (p = 0.016), and lymph node metastasis (0.04). Conclusions EMT and cancer stem cell IHC markers are biomarkers for aggressive tumour growth and lymph node metastasis.Hence, EMT markers (E-cadherin and beta-catenin) and cancer stem cell markers (CD44) can be used as prognostic markers.

Abstract IA006: The effect of ancestry and the genomics of colorectal cancer: Implications on incidence and outcomes

Abstract Blacks have a higher incidence of colorectal cancer (CRC) and worse survival rates when compared to Whites. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer MSI-H tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations specifically KRAS G12D and KRAS G13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, RET). In patients with young onset CRC (&amp;lt;50 years), AFR and EUR had similar frequency of MSI-H and TMB-H tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of our diverse US population. Further studies are needed to investigate the role of colon polyps and the effect of genomics, ancestry and social determinants of health on CRC incidence and outcomes. Citation Format: Parvathi A. Myer. The effect of ancestry and the genomics of colorectal cancer: Implications on incidence and outcomes [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA006.

Usefulness of BRAF VE1 immunohistochemistry in non-small cell lung cancers: a multi-institutional study by 15 pathologists in Korea.

Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non-small cell lung cancers (NSCLCs). A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images. In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

Expression and Prognostic Role of CXCL1 Gene in Colorectal Adenocarcinoma.

In this manuscript, we have extensively examined expression and prognosis of CXCL1 gene in colorectal adenocarcinoma (COAD) using different cases of colorectal adenocarcinoma and tissues. To verify this, protein and mRNA expressions of cxcl1 were identified through RT-PCR and immunohistochemistry in 30 cases of colorectal adenocarcinoma and adjacent tissues, which were surgically resected from January to July 2021 in our hospital, and relationship between CXCL1 mRNA and clinicopathological features and protein expression was analyzed. CXCL 1 mRNA in COAD carcinoma's expression was considerably higher than in the adjacent normal intestine. At the same time, CXCL 1 diagnostic receiver operating characteristic (ROC) curve had preferably higher value of the diagnostic for area under curve (AUC) = 0.912, 95%, COAD (P < 0.001, CI = 0.825–0.969). We have observed that CXCL1 gene was closely linked with preoperative CEA level (P=0.007) and gross tumor typing (P=0.039). Finally, we have concluded that that CXCL1 can be a possible biomarker for stress prognosis and diagnosis.

CDX2 immunohistochemical expression in human colorectal adenocarcinoma and gastric adenocarcinoma: A comparative study

Background: Caudal-related home box gene two (CDX2) is home box domain containing transcription factor that is important in the development and differentiation of the intestine. Aim of the study: to examine the expression of Caudal-related home box gene two in a series of colorectal and gastric adeno carcinomas, and correlate its expression with different clinic pathological parameters including: tumor type grade stage and compare its expression between the two malignancies. Material and Method: this is a retrospective study of a total of fifty cases including twenty five cases of colorectal carcinomas and twenty five cases of gastric adenocarcinoma were collected from the histopathology laboratory department of gastroenterology and hepatology teaching in Baghdad (from January 2021 to January 2022); slides were prepared from paraffin blocks and stained with Hematoxylin and Eosin for histopathological revision and others were stained immunohistochemically with CDX2, CDX2 expression was semi-quantitatively scored. Correlation between clinic pathological parameters and CDX2 expression was done. Results: Regarding the twenty-five cases of colorectal adenocarcinoma: age range was (45-85) years,15 (60%) of cases were males, 10 (40%) of them were females, most common cases 23 (92%) were grade 2, and most common 18 (72%) of the cases were stage T3, most common cases 16 (64%) cases had no lymph node involvement (N0), all the cases showed positivity for or CDX2,17 (68%) of cases had CDX2 score (3) while 8 (32%) of them had CDX2 score (2). Regarding the twenty five cases of gastric adenocarcinoma: age range was (24-69) years,17 (68%) of were males, 8 (32%) of them were females, most common 14 (56%) of the cases were grade (2), and most common stage 20 (80%) of the cases were stage T3,most common cases 7 (28%) had no lymph node involvement (N0), most 15 (60%) of the cases showed positivity for or CDX2, 9 (36%) of cases had CDX2 score (1), 5 (20%) of cases showed score (2),1 (4%) of cases showed score (3), while 10 (40%) of the cases were negative for CDX2 (score 0). Conclusion: CDX2 marker is already proven as highly sensitive in colorectal adenocarcinoma. There was a significant correlation between CDX2 score and the site of the tumor (colorectal versus gastric).

RELATIONSHIP OF DIRTY NECROSIS WITH HISTOPATHOLOGICAL GRADING IN COLORECTAL ADENOCARCINOMA

Background: Dirty necrosis (Intraacinar necrosis/garland necrosis) is defined as the presence of cell remnants in the lumen of the gland. Dirty necrosis consisting of an eosinophilic mass, which is a mass originating from the cytoplasm of dead cells mixed with the remnants of the cell nucleus. The remnants of the cell nucleus are blue and the eosinophilic mass is pink in the background. Dirty necrosis results from the breakdown of carcinoma cells, which usually accumulate in the lumen of intact tubular glands, and may be associated with spontaneous events involving insufficient tumor vascular supply. Assessment of the presence of a dirty necrosis is considered a characteristic of colorectal carcinoma. Objective: This study was conducted to analyze the relationship between dirty necrosis and histopathological grading of colorectal adenocarcinoma. Methods: The study used 55 paraffin block samples of colorectal adenocarcinoma cases that had been diagnosed at the Anatomical Pathology Laboratory, H. Adam Malik Hospital, Medan and at the Anatomical Pathology Laboratory, Faculty of Medicine, Universitas Sumatera Utara, since 2019-2020. Dirty necrosis was assessed using H&E staining with 400x magnification assessed over the entire lumen of the gland, if <10% was considered absent and if >10% was considered present. Results: The results showed that there were 47 samples (85.4%) of dirty necrosis, while 8 samples (14.6%) did not. For the most histopathological grading, 42 samples (73.4%) were low grade, while the high grade was 13 samples (23.6%). Statistical tests between dirty necrosis and colorectal adenocarcinoma histopathological grading showed no significant relationship with p value = 0.376 (p >0.05). Conclusion: There was no statistically significant relationship between dirty necrosis and histopathological grading in colorectal adenocarcinoma.

The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer.

Omshree ShettyVikas OstwalIntroduction The present study evaluates the mutation pattern and frequency of BRAF , PIK3CA and RAS in colorectal carcinoma observed in the tertiary cancer center in India. Materials and Methods Consecutive cases of colorectal adenocarcinoma ( n = 330) registered from January 2015 to December 2019 (5-year duration) were selected for the study. Molecular analysis for BRAF . PIK3CA (exon 9 and 20) and RAS ( KRAS & NRAS ) was performed on representative formalin-fixed paraffin-embedded tissues by Sanger sequencing. Results were correlated with clinicopathological features. Patient overall survival (OS) was obtained using Kaplan-Meier method. Results The study cohort was in the age range of 22 to 81 years (median age: 52 years) that included 202 males and 96 females (male: female ratio 2.1:1). BRAF V600E mutation was observed in three cases (1%), while 17 cases (5.7%) had mutations in the PIK3CA gene (exon 9 or exon 20). Mutation analysis for RAS gene ( KRAS & NRAS ) was observed among 42 (15.4%) cases with KRAS mutation and 11 (4%) cases were positive for NRAS mutations. Among RAS, KRAS G12D was the predominant mutation. Median OS with wild-type RAS was 46.6 months (95% confidence interval [CI]: 22.4-70.8), while for RAS mutated patients, it was 25.6 months (95% CI: 16.7-34.5), hazard ratio: 1.7 (95% CI: 1.1-2.7, p = 0.025). Conclusion This study evaluated the prevalence of BRAF, PIK3CA and RAS mutations in the Indian cohort and its impact on clinical behavior. There was lower incidence of BRAF mutations in this cohort and PIK3CA mutation (single) did not impact survival of the patients.

Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer.

BackgroundThe relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized.MethodsIn 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias.ResultsImmature desmoplastic reaction was associated with lower densities of intraepithelial CD3+CD8+CD45RO+ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29–0.62; Ptrend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28–0.70; Ptrend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3+CD8+CD45RO+ cells (Ptrend <0.0001) and stromal M1-like macrophages (Ptrend = 0.0007)] and for keloid-like collagen bundles (Ptrend <0.0001 for intraepithelial CD3+CD8+CD45RO+ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23–0.44; Ptrend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16–0.39; Ptrend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05–0.28; Ptrend <0.0001) for absent (vs. marked) keloid-like collagen bundles.ConclusionsImmature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.

The Genomics of Colorectal Cancer in Populations with African and European Ancestry.

KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC. See related commentary by Eng and Holowatyj, p. 1187. This article is highlighted in the In This Issue feature, p. 1171.

Yolk Sac Tumor in a Recurrence of Colonic Adenocarcinoma With Shared Mutations inAPCandTP53Genes: A Case Report

Only four cases of colorectal adenocarcinoma with a yolk sac tumor (YST) component have been reported in the English literature. No genetic investigation has been performed in these cases. We report a case of colorectal adenocarcinoma in which the recurrent tumor had a YST component. A 49-year-old woman presented with a pelvic tumor three years after endoscopic mucosal resection of sigmoid colon adenocarcinoma. The pelvic tumor consisted of an undifferentiated carcinoma component and a YST component. The serum alpha-fetoprotein level was elevated to 42 ng/mL. Treatment as conventional colorectal carcinoma produced some anticancer effects, but the patient died 14 months after the recurrence and 49 months after the EMR. With the help of the next-generation sequencing results of the recurrent tumor, APC c.835 - 8A > G and TP53 c.524G > A (p.R175H) mutations were identified by direct sequencing in both the primary and the recurrent tumors, confirming the relationship between the two metachronous tumors.