Cases Of Colorectal Carcinoma Research Articles

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.

Il-6 and MSH3 in colorectal carcinoma: Expression, relationship, and prognostic significance in 171 colorectal carcinoma cases.

Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence.

It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.

Surgical interventions of colon cancer

Colon cancer is most common type of malignancies all over the world. Various risk factors including genetic mutations,old age,family history, smoking, drinking excessively, poor diet and several others are associated with increasing cases of colorectal carcinoma(CRC). Diagonosis is usually made by colonoscopy and and confirmed by tissue biopsy. After diagonosis delay to treatment can worsen the disease progression and long-term outcome.Treatment options for CRC include surgical resection either open or laparoscopic both with their merits and demerits. Laparoscopic resection have been well accepted for treatment and is known to result in less hospitalisation and blood loss while open surgery still has same overall survival rate, morbidity and mortality. Surgical treatment is associated with postoperative complications including port site metastases, surgical site infections (SSIs),Adhesions, intestinal obstruction, venous thromboembolic events, colonic ischemia, these complications can be decreased by preoperative assessment, intraoperative care and postoperative interventions. Controlling nutritional status (COUNT) score is prognostic factor of postoperative complications and mortality of patients with CRC. 5-years survival rate has increased upto 70% due to improved treatment modalities.

Insights from a retrospective study: an understanding of pediatric colorectal carcinoma

Pediatric colorectal cancer, comprising just 1% of childhood cancers, has surged among young individuals, underscoring its significant health impact. Diagnostic challenges arise from atypical presentation and nonspecific symptoms in 90% of cases, leading to delayed detection in 19%.Methods A 2-year retrospective study of pediatric colorectal carcinoma cases was conducted across a specialized surgical pediatric center. Data were gathered, including age, symptoms, diagnostics, treatments, and outcomes.Results Six colorectal carcinoma cases (median age, 16) were documented, mainly in males (66%). Predominant histological types included mucinous adenocarcinoma and signet ring cell carcinoma. Metastasis was present in all cases, with symptoms including hematochezia (83%), abdominal pain (100%), weight loss (66%), and anemia (100%). Diagnosis often faced misidentification, fostering disease progression and metastasis. Various diagnostic and treatment modalities were employed, including surgery and neo-adjuvant or adjuvant chemotherapy.Conclusion Swift detection and intervention for pediatric colorectal carcinoma are pivotal. Efficient diagnostics and heightened awareness among medical professionals and the public are imperative. Early surgical intervention remains a cornerstone, especially for patients with pertinent family histories and characteristic symptoms. Tailored guidelines for pediatric patients are needed to enhance outcomes and survival.

BRAFV600E immunohistochemistry can reliably substitute BRAF molecular testing in the Lynch syndrome screening algorithm in colorectal cancer.

The Lynch syndrome (LS) screening algorithm requires BRAF testing as a fundamental step to distinguish sporadic from LS-associated colorectal carcinomas (CRC). BRAF testing by immunohistochemistry (IHC) has shown variable results in the literature. Our aim was to analyse concordance between BRAFV600E IHC and BRAF molecular analysis in a large, mono-institutional CRC whole-slide, case series with laboratory validation. MisMatch repair (MMR) protein (hMLH1, hPMS2, hMSH2, and hMSH6) and BRAFV600E IHC were performed on all unselected cases of surgically resected CRCs (2018-2023). An in-house validation study for BRAFV600E IHC was performed in order to obtain optimal IHC stains. BRAFVV600E IHC was considered negative (score 0), positive (scores 2-3), and equivocal (score 1). Interobserver differences in BRAFV600E IHC scoring were noted in the first 150 cases prospectively collected. Nine-hundred and ninety CRCs cases (830 proficient (p)MMR/160 deficient (d)MMR) were included and all cases performed BRAFV600E IHC (BRAFV600E IHC-positive 13.5% of all series; 66.3% dMMR cases; 3.4% pMMR cases), while 333 also went to BRAF mutation analysis. Optimal agreement in IHC scoring between pathologists (P < 0.0001) was seen; concordance between BRAFV600E IHC and BRAF molecular analysis was extremely high (sensitivity 99.1%, specificity 99.5%; PPV 99.1%, and NPV 99.5%). Discordant cases were reevaluated; 1 score 3 + IHC/wildtype case was an interpretation error and one score 0 IHC/mutated case was related to heterogenous BRAFV600E IHC expression. Among the 12 IHC-equivocal score 1+ cases (which require BRAF molecular analysis), three were BRAF-mutated and nine BRAF-wildtype. BRAFV600E IHC can be used as a reliable surrogate of molecular testing after stringent in-house validation.

Role of HER2/neu in Colorectal Carcinoma: A Cross-sectional Study from a Tertiary Care Centre in West Bengal, India

Introduction: In many tumours, Human Epidermal Growth Factor Receptor 2 (HER2) expression and HER2 amplification are studied as therapeutic and prognostic factors. The incidence of HER2/neu expression and its consequences in patients with colorectal carcinoma has shown conflicting evidence. Aim: To evaluate the utility of HER2/neu expression in colorectal carcinoma and to find any association between HER2/neu expression, histological grade, and stage of the tumour. Materials and Methods: This cross-sectional study was conducted on 50 cases of colorectal carcinoma. Patients undergoing surgery for colorectal tumours were selected over an 18-month period (January 2020 to June 2021) in a tertiary care hospital in Kolkata, West Bengal, India. Various clinical and demographic parameters were obtained from the patients, and the specimens were subjected to Immunohistochemical (IHC) staining for HER2/neu. The results were analysed using Statistical Package for the Social Sciences (SPSS)software version 25.0 (IBM, Armonk, New York, USA). Results: On HER2/neu IHC examination, 30 cases (60%) showed a 3+ score, 4 cases (8%) showed a 2+ score, 7 cases (14%) showed a 1+ score, and the remaining 9 cases (18%) showed a score of 0. HER2/neu expression was found in 30 cases (60%) of colorectal carcinoma. HER2/neu expression showed a significant association with the histological grade of the tumour (p-value=0.020). HER2/neu expression also showed a significant association (p-value&lt;0.001) with histological subtypes of the tumour. Conclusion: This study revealed a significant association between HER2/neu expression and histological subtypes and grade of the tumour. Moderately differentiated adenocarcinoma showed the highest expression, while mucinous adenocarcinoma and undifferentiated carcinoma showed minimal or absent HER2/ neu expression. Thus, HER2/neu can serve as a prognostic and therapeutic marker in colorectal carcinoma. In conclusion, surgery alone is not curative for patients with colorectal cancer, and additional forms of management may be required to improve patient survival. In such cases, HER2/neu expression can guide new adjuvant therapy.

CORRELATION OF LEPTIN AND ADIPONECTIN RECEPTOR EXPRESSION WITH CLINICOPATHOLOGICAL PARAMETERS IN COLORECTAL CARCINOMA - A CROSS-SECTIONAL PROSPECTIVE STUDY.

Colorectal carcinoma (CRC) is one of the common carcinomas with a rising incidence of metastasis due to its advanced stage of presentation. The existing biomarkers such as CEA (Carcinoembryonic antigen) etc., for prognosis, have low sensitivity and specificity. Hence a need for a newer definitive biomarker. Obesity is the leading cause of CRC. Leptin and adiponectin secreted by adipose tissue have been studied as potential biomarkers in the field of CRC. The present study helps to understand the association of leptin and adiponectin receptors with clinicopathological parameters. To correlate the various clinicopathological parameters with the tissue expression of leptin and adiponectin receptors in CRC. It is a cross-sectional prospective study conducted at a tertiary care hospital. Formalin fixed paraffin blocks of all radical resection CRC cases were collected and immunohistochemistry (IHC)was carried out on tumor tissue for leptin and adiponectin receptor. Tumor characteristics and clinical parameters were collected from the hospital medical records. Pearson's correlation coefficient test was used. Immunohistochemistry was performed on 60 cases of CRC. Significant positive correlation of leptin was observed with size, lymph node metastasis, advanced stage, and grade of tumor (P<0.05). A significant correlation between adiponectin receptor and CRC was observed concerning age, stage, lymph node metastasis, distant metastasis and grade of tumor. Positive expression of leptin and negative expression of adiponectin receptors in CRC helps to predict the risk of metastasis.

IMMUNOHISTOCHEMICAL EXPRESSION OF THYMIDYLATE SYNTHASE IN DIFFERENT GRADES OF COLORECTAL CARCINOMA

Objective: To Evaluate the Immunohistochemical Expression of Thymidylate Synthase in different grades and histological types of Colorectal Carcinoma.&#x0D; Study Design: Cross sectional, Descriptive study&#x0D; Place and duration of study: This study was conducted from June 2019 to November 2020 in the Department of Pathology at Postgraduate Medical Institute Lahore / Lahore General Hospital. &#x0D; Methodology: Forty resected gut specimens diagnosed on light microscopy as Colorectal adenocarcinoma were included on the basis of non-probability, consecutive sampling technique. Cases were reviewed and histological typing and grading was done separately by two competent Histopathologists. Immunohistochemical staining for Thymidylate Synthase was performed. Results of Thymidylate Synthase immunostaining were interpreted by the two observers based on the cytoplasmic staining of tumor cells. Thymidylate Synthase expression was quantified through a visual grading system depending upon the staining intensity and percentage of stained cells. &#x0D; Results: Out of 40 cases of adenocarcinoma, majority of the patients (45%) belong to the age range of 51-60 years. There were 31(77.5%) male patients while 9(22.5%) were females. 28 (22%) cases were classified as low grade while 12 (11%) cases were reported as high-grade carcinomas. Amongst these Thymidylate Synthase expression was seen in 78.6% of low-grade carcinoma and 91.6% of high-grade carcinomas. Regarding histological subtyping, 23(57.5 %) cases were identified as non-mucinous adenocarcinomas, (9)22.5% as mucinous adenocarcinoma and (8) 20% as signet ring adenocarcinoma. Thymidylate Synthase expression was found to be similar i.e., 78% in non- mucinous as well as mucinous carcinomas however, 100% positivity was noticed in signet ring carcinomas. The overall positivity for Thymidylate Synthase was found to be 82.5%. &#x0D; Conclusion: Colorectal carcinoma was prevalent among males of 51-60 years of age. 82.5% cases of colorectal carcinoma expressed Thymidylate synthase receptors and its expression was found to be higher in high grade tumors.&#x0D;

Prognostic potential of MNX1-AS1 in chemotherapy of colorectal carcinoma.

To clarify the role of MNX1-AS1 in 5-FU resistance of Colorectal carcinoma (CRC). Relative levels of MNX1-AS1 in CRC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Recruited CRC patients were treated by 5-FU-based FOLFOX chemotherapy, and they were divided to effective group and non-effective group according to the therapeutic efficacy, followed by comparison of their differences in clinical indicators. Influences of MNX1-AS1 on clinical features of CRC were analyzed. In addition, in vitro level of MNX1-AS1 in 5-FU-resistant HCT-8 cells and their parental cells was detected. After knockdown of MNX1-AS1 in HCT-8/5-FU cells, viability change was evaluated by cell counting kit-8 (CCK-8) assay. At last, regulatory effects of MNX1-AS1 on expression levels of ABC family genes were detected. MNX1-AS1 was upregulated in CRC tissues than paracancerous ones, and its level was higher in 5-FU-resistant CRC cases in comparison to 5-FU-sensitive cases. MNX1-AS1 level was linked to tumor size, tumor differentiation, depth of invasion, TNM staging and lymphatic metastasis in CRC. Notably, TNM staging, depth of invasion and lymphatic metastasis could affect the efficacy of FOLFOX chemotherapy in CRC patients. Knockdown of MNX1-AS1 reduced viability in HCT-8/5-FU cells, and downregulated ABCA1, ABCB1, ABCC1, ABCG1 and ABCG2. MNX1-AS1 triggers 5-FU resistance in CRC cells. Knockdown of MNXK1-AS1 is conductive to the well response to FOLFOX chemotherapy in CRC patients.

Grades of Poorly Differentiated Clusters are Associated with Lymph Node and the Tumour, Node and Metastasis Stages in Colorectal Carcinoma.

Colorectal carcinoma (CRC) is the third most common cancer globally. In Malaysia, CRC is most prevalent among males and the second most common cancer among females. The CRC arises mainly from the adenocarcinoma sequence. Poorly differentiated clusters (PDCs) and tumour budding (TB) are believed to represent sequential steps in tumour growth. Therefore, this study analysed the association between PDC grades with clinicopathological and demographic characteristics of CRC. A total of 47 CRC cases previously diagnosed by histopathological examination were reviewed for the presence of PDCs and graded accordingly. The association between PDC grades with clinicopathological and demographic characteristics was statistically analysed. Out of the 47 cases with PDCs, most of them were of grade 3 (G3) (n = 27, 57.4%), followed by grade 2 (G2) (n = 13, 27.7%) and grade 1 (G1) (n = 7, 14.9%). Higher PDC grades (G2 and G3) were mainly observed in higher tumour stage (T); T3 (n = 26, 83.9%), T4 (n = 12, 92.3%), N1 (n = 20, 86.9%), N2 (n = 15, 100%). In addition, there was a significant association between PDC grades with the nodal stage (N) (P = 0.013) and the tumour, node and metastasis (TNM) stages (P = 0.012). The PDC grades are useful for assessing the disease prognosis in CRC. A statistically significant association between PDC grades with N and TNM stages suggested that PDC grades are potential predictive parameters for invasive and metastatic risks in CRC.

Evaluation of HHLA2 and CD8 Immunohistochemical Expression in Colorectal Carcinoma and Their Prognostic Significance.

Colorectal carcinoma (CRC) is the third most common malignancy worldwide. Human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2) is a novel immune checkpoint molecule. The association between HHLA2 expression and clinicopathological features and its prognostic significance in CRC patients are still controversial. The aim of this study is to evaluate the prognostic value of immunohistochemical (IHC) expression of HHLA2 and CD8 in CRC. This retrospective study included 134 cases diagnosed with primary CRC at the Gastrointestinal Surgery Center (GISC) department, Mansoura Faculty of Medicine, during the period from December 2014 to December 2018. Clinicopathological and survival data were collected. IHC for HHLA2 and CD8 was performed, and they were correlated with clinicopathological parameters and patient prognosis. Among 134 CRC cases, high HHLA2 expression was detected in 73 (54.5%). High HHLA2 expression was significantly related to the depth of invasion (P = 0.005*), lymph node metastasis (P = 0.01*), tumor stage )P = 0.002*), and distant recurrence )P = 0.012*). Multivariate analysis spotted HHLA2 high expression as an independent prognostic predictor for OS in CRC (P = 0.03*) and DFS (P = 0.008*). CD8 shows a significant correlation with tumor infiltrating lymphocytes (TILs) (P ≤ 0.001*), absence of metastasis ((P = 0.029*), absence of tumor deposits (P=0.014*). However, CD8 shows no significant association with survival or HHLA2. HHLA2 is an independent prognostic factor for the overall survival and disease free survival of CRC patients and can predict poor prognosis in CRC patients.

Utility of CD34 in Assessing Microvessel Density and Its Correlation With Clinicopathological Parameters in Colorectal Carcinoma Patients.

Currently, the most commonly practiced method of reporting cases of colorectal carcinoma is done according to guidelines provided by the College of American Pathologists (8th edition) and the Royal College of Pathologists (UK). These guidelines include various histopathological parameters like tumor site, extent, histologic type, grade, margins, tumor budding, lymphovascular invasion, and perineural invasion. However, in the present guidelines, the immunohistochemistry-based marker of mean vessel density (MVD) has not been addressed as an important parameter. The present study gives an overview of the importance of MVD.MVD was statistically significant when correlated with tumor size, lymph node metastasis, grade, and vascular invasion. However, no statistical significance was observed when compared with age, perineural invasion, and stage of the tumor.

Invasive stratified mucin-producing carcinoma of the colorectum: expanding the morphologic spectrum of large bowel cancer

BackgroundInvasive stratified mucin-producing carcinoma is a recently recognized adenocarcinoma with distinctive features. It was first described in the cervix but similar tumors have since been reported in the penis, anus and prostate. In the gastrointestinal tract, the phenomenon of epithelial stratification has an interesting embryologic morphogenesis. Gastrointestinal mucosa starts off as nascent columnar epithelium that is subsequently patterned to confer regional specific functions. However, in disease states, normal architectural patterning can be disrupted by aberrant differentiation. Given this background and the phenotypic plasticity of neoplastic cells, we were interested in ascertaining whether invasive stratified mucin-producing carcinoma occurs in the colorectum.MethodsThis was a retrospective study of all 584 cases of colorectal carcinoma accessioned at our institution over a 2-year period (January 2021- December 2022). Cases were analyzed to determine which fulfilled the criteria for invasive stratified mucin-producing carcinoma.ResultsThere were 9 cases of colorectal invasive stratified mucin-producing carcinoma—one pure form and 8 mixed. They showed the classic colorectal (CK20 + , CDX2 + , CK7-) immunostaining profile but, based on various morphologic criteria, they could be distinguished from conventional adenocarcinoma NOS, mucinous, signet ring cell, medullary, goblet cell and undifferentiated carcinomas. About half the cases were MLH1/PMS2 deficient and BRAF &/or PIK3CA mutated, which aligns with the hypermutated phenotype.ConclusionsColorectal invasive stratified mucin-producing carcinoma appears to be a real entity, best recognized in its early stages. It appears to be a high-grade carcinoma. With tumor progression, it evolves into a mucinous adenocarcinoma with a proclivity towards signet ring cells. In summary, the study of this tumor, particularly in its early stages, provides useful clues to further understanding the biology and progression of large bowel cancer. Further studies are required to learn more about this tumor.

Tumor budding in colorectal adenocarcinoma using cytokeratin 20 immunostaining

Introduction: Colorectal cancer is the third most common cancer worldwide and second most common fatal cancer. Tumor budding is an emerging prognostic indicator in cancers. Though tumor budding can be assessed using Hematoxylin and Eosin stain, sometimes peritumoral inflammation and reactive stromal fibrosis obscures the tumor buds. The present study aimed to assess tumor budding using cytokeratin 20 immunohistochemistry in colorectal cancers. Methods: This is a cross sectional study which included 30 cases of colorectal carcinomas. cytokeratin 20 stained slides of colorectal carcinoma were assesed for tumor budding using International Tumor Budding Consensus Conference (ITBCC) 2016 consensus criteria and compared with AJCC cancer stage. Results: Demographic analysis showed peak incidence of colorectal cancer in the age group of 55-64 years (33.3%) and male: female ratio of 1.14:1. Majority of the tumors with score 1(23.3%) showed stage I. While tumors with score 2 had similar incidence of stage I (16.6%) and II (16.6%) and lesser incidence of stage III (3.33%). Most of the tumors with score 3 tumor budding had stage III tumors (26.67%). The p value is &lt; 0.0001, which is statistically significant. Tumor budding signifies the biological and molecular phenomenon of epithelial-mesenchymal transition in the tumor microenvironment. Loss of E-cadherin, alterations in transcription factors including SNAIL, ZEB, TWIST etc and switching of CMS2 to CMS4 are some of the recorded molecular profiles responsible for tumor budding. Conclusion: This study concludes that the tumor stage increases with tumor budding and thus is a reliable marker in predicting the prognosis. This study also states that immunohistochemical study gives objective scoring of tumor buds in colorectal cancers. Keywords: tumor budding; colorectal cancer; cytokeratin 20; prognostic marker

Evaluation and Clinicopathological Correlation of ALDH1 in Colorectal Adenoma with Low-/High-Grade Dysplasia and Carcinoma.

Colorectal carcinoma (CRC) stands as one of the most prevalent malignant neoplasms, carrying significant morbidity and mortality implications. Within colorectal carcinogenesis, cancer stem cells are recognized as key contributors, infusing tumors with aggressive traits, including chemoresistance. A group of enzymes known as ALDH1 exhibits stem cell properties, potentially playing a role in colorectal neoplasms. This study aims to evaluate ALDH1 expression in colonic neoplasms and its correlation with clinicopathological parameters. The research encompasses 50 consecutive cases, involving CRC (30) and colorectal adenoma (20), gathered prospectively from September 2019 to August 2021, as well as archived cases from January 2018 to August 2019. Histological examination was conducted on CRC cases to assess tumor type, grade, lymphovascular invasion, perineural invasion, mitosis, and necrosis, while colorectal adenomas were subjected to histological grading. ALDH1 immunohistochemistry was performed on both CRC and adenoma specimens. Statistical analysis utilized SPSS 20 software, employing the chi-squared test and Fischer's exact test. A higher count of adenoma cases displayed positive staining (p = 0.0005) and greater expression (p = 0.036) in comparison to carcinoma cases. The other clinicopathological parameters didn't demonstrate notable associations. Adenomas with low-grade dysplasia exhibited a higher frequency of positive ALDH1 staining and expression than those with high-grade dysplasia. In malignant cases, a higher proportion of positive staining was observed in lower-stage disease compared to higher-stage disease. The heightened staining and expression outcomes of ALDH1 in adenomas versus carcinomas, as well as their presence in lower-stage carcinomas, suggest the potential acquisition of novel mutations and the proliferation of distinct clonal stem cell subsets during disease progression. The absence of ALDH1 in adenoma/carcinoma could indicate a poorer prognosis and an increased likelihood of disease progression to a higher stage. Comprehensive multi-institutional and validation studies are needed to enhance our understanding of ALDH1's role in colorectal oncogenesis, as well as its viability as a targeted or personalized therapy option.

Expression of Interleukin 23p19 in Colorectal Carcinoma: An Immunohistochemical Study with Clinico-Pathological Correlation

Background Cancer of the colon is the fourth most common cancer in the world, while cancer of the rectum is the eight most common. Together, colorectal carcinomas (CRCs) are the third most commonly diagnosed form of cancer globally, comprising about 11% of all cancer diagnoses. In Egypt, a rapid increase in CRC incidence has been observed with an unusually high rate under the age of 40. Interleukin 23 (IL-23) is a member of a family of pro-inflammatory cytokines, consisting of a p19 subunit and a p40 subunit. Studies showed that IL-23 signaling causes up-regulation of MMP9, increased angiogenesis, and reduced CD8+ T cell recruitment to tumors. Therefore, IL-23–mediated inflammatory processes might provide a tumor-promoting microenvironment. Objective To evaluate the immunohistochemical expression of IL23p19 in colorectal carcinoma with clinico-pathological correlation. Methods This is a retrospective study consisting of formalin fixed paraffin embedded tissue blocks of 25 cases diagnosed as colorectal carcinoma. All tissue blocks were retrieved from the archives of the pathology department at Al-Demerdash Hospital. Results There was a significant difference between CRC cases with different tumor stages as regard total IL23p19 expression, as 100% of cases with higher stage (T4a/b) had positive expression compared to 42.9% and 92.9% of T2 and T3 respectively. However, no significant difference was detected between cases with different tumor grades as regard total IL23p19 expression. Conclusion It can be concluded from our study that there is an association between IL23p19 expression and the pathological stage in CRC patients. IL23p19 could be used as a prognostic biomarker and a potential treatment target.

Analysis of Histological Prognostic Factors in Colorectal Carcinoma and Relationship of VEGF and E-Cadherin Expression in Prognostic Assessment

Colorectal carcinomas (CRC) are associated with several histopathological and molecular factors of prognostic and hence therapeutic implications, including for epithelial mesenchymal transition (EMT) and angiogenesis. Downregulation of E-cadherin is a crucial step in EMT, directly related to tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) induces angiogenesis and thereby tumour progression and metastases. Our objective was to analyse VEGF and E-cadherin expression in patients with CRC and to effectively assess the relationship of these with histopathological factors. 50 cases of CRC obtained over eighteen months duration, were included in the study. Haematoxylin and Eosin-stained sections were studied for histopathological factors. Immunohistochemistry with E-Cadherin and VEGF were performed on representative sections and evaluated. Histopathological features of importance noted were low grade tumour budding (55.5%), Infiltrative invasive front (83%), lympho-vascular invasion (50%). Preserved expression of E-Cadherin was seen in 66% of the cases, and 34% reduced expression, predominantly noted in patients above the age of 50, increased tumour size, mucinous variants, advanced TNM stage, lymph node involvement and high-grade tumour budding. VEGF staining was seen in 64% of the cases with varying intensity. Increased VEGF expression was noted in poorly differentiated tumours, advanced Duke’s stage and with lymph node metastasis. Colorectal carcinomas with high grade tumour budding were associated with lymph vascular invasion, infiltrative invasive front and significantly correlated with TNM stage. High grade tumours and adverse histopathological prognostic factors revealed a reduced E-cadherin expression and increased VEGF expression.

Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice.

Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2-3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI+) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been recently demonstrated that the overexpression of certain microRNAs (miRNAs, miRs), such as miR-155, miR-21, miR-137, can induce MSI or modulate the expression of the genes involved in LS pathogenesis. MiRNAs are small RNA molecules that regulate gene expression at the post-transcriptional level by playing a critical role in the modulation of key oncogenic pathways. Increasing evidence of the link between MSI and miRNAs in LS prompted a deeper investigation into the miRNome involved in these diseases. In this regard, in this study, we discuss the emerging role of miRNAs as crucial players in the onset and progression of LS as well as their potential use as disease biomarkers and therapeutic targets in the current view of precision medicine.

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters.

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of twoyears. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.