Cases Of Colorectal Carcinoma Research Articles

Routine Elastic Staining Helps Detection of Vascular Invasion in Colorectal Cancer: A Comprehensive Analysis of T3 or Higher Tumors Without Lymph Node Metastasis.

Vascular invasion (VI) in colorectal carcinoma (CRC) is an independent prognostic feature and a high-risk indicator for adjuvant chemotherapy in stage II CRC. This study evaluated the effect of elastic staining on VI detection. The VI was assessed using elastic staining in 154 patients with CRC. Based on hematoxylin and eosin (H&E) staining, cases were classified into three groups: absent (n=80), equivocal (n=23), and suspected (n=51). Two sections per case were evaluated for VI using elastic staining, and the presence of VI on one or both slides was confirmed. Finally, the correlation between the VI and other clinicopathological factors was analyzed. The overall detection rate of VI using elastic staining was 67/154 (51.4%). VI was detected in 17/80 (21.3%), 3/23 (13.0 %), and 47/51 (92.2%) patients in the absent, equivocal, and suspected groups, respectively. VI was detected in both sections of the elastic staining slides in 28 cases, and in only one section in 38 cases. The VI was significantly associated with perineural invasion, M stage, and synchronous metastasis. VI detection using H&E staining alone is not reliable, emphasizing the importance of elastic staining in improving VI detection. Therefore, we recommend the incorporation of elastic staining into routine pathological practice for all pT3 and pT4 CRC cases.

Characterizing POLE Mutation-Associated Colorectal Carcinoma: Clinical and Pathologic Insight

Abstract Introduction/Objective Colorectal carcinoma (CRC) is one of the most common cancers and a leading cause of cancer-related death in the United States. Pathogenically, colorectal carcinoma is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alteration. Identification of DNA polymerase mutation leads to the characterization of a new molecular pathway of carcinogenesis named the POLE pathway. Methods/Case Report Utilizing the cBioportal platform and Cancer Genome Atlas (TCGA) Firehouse Legacy data, we identified 118 cases of CRC with mutations in the POLE gene. We evaluated the various clinical and pathologic features of POLE mutation-associated CRC. Results (if a Case Study enter NA) Within the cohort of 118 cases linked to mutations in the POLE gene, gender distribution reveals that 63 individuals, comprising 53.8% of the sample, are male, while 42 individuals, accounting for 35.9%, are female. Ethnicity breakdown showcases a predominantly White population, with 92 cases (78.6%), followed by 8 cases (6.8%) attributed to Asian-Far East/Indian Subcontinent descent, 5 cases (4.3%) categorized as Asian, and 4 cases (3.4%) each identified as Black and Black or African American. Additionally, one case (0.9%) has an unknown ethnicity, while 4 cases (3.4%) have unspecified racial backgrounds. The average age at diagnosis is recorded at 48.5 years, with ages ranging from 25 to 85, signifying a broad age spectrum within the affected population. Delving into cancer subtypes, the majority of cases, constituting 64 instances (54.2%), manifest as colon adenocarcinoma, while 38 cases (32.2%) present as rectal adenocarcinoma. Moreover, 9 cases (7.6%) are characterized as colorectal adenocarcinoma, 6 cases (5.1%) are classified as mucinous adenocarcinoma of the colon and rectum, and one case (0.8%) manifests as medullary adenocarcinoma of the colon. This detailed elucidation provides a comprehensive understanding of the demographics and clinical presentation within the cohort affected by POLE gene mutations. Conclusion In summary, our research has meticulously examined 118 instances of colorectal carcinoma (CRC) intricately linked to mutations in the POLE gene. Within this cohort, a predominant demographic emerges, with a notable prevalence among individuals of White ethnicity. Delving deeper into the pathological spectrum, colon adenocarcinoma emerges as the prevailing subtype, exemplifying the intricate interplay between genetic aberrations and cancer manifestation.

Significance of CD70, VEGF, and CD90 Immunohistochemical Expression in Colorectal Cancer.

Colorectal cancer is the 4th most reported reason for cancer death worldwide. It is a complex and multifaceted disease with diverse histopathological manifestations. CD70 is present on activated immune cells and is upregulated in patients who have finished adjuvant therapy. VEGF controls angiogenesis and demonstrates immuno-regulatory characteristics that inhibit the anticancer activity of immune cells. CD90 is an extracellular cancer stem cell marker and regulates apoptosis, cell migration, and T cell activation. to elucidate the prognostic potential of a combined immunohistochemical assessment of CD70, VEGF, and CD90 biomarkers in colorectal cancer tissues. Our study is a retrospective study done on 70 paraffin blocks (45 colorectal carcinoma cases and 11 adenomas, along with 14 cases of colitis serving as controls) were subjected to conventional Hematoxylin and Eosin stain for routine histopathological assessment and immunohistochemical staining for CD70, VEGF and CD90. Our investigation focused on evaluating the expression of CD70, VEGF, and CD90 in various colorectal tissues, including colitis, adenomas, and adenocarcinomas, as well as different grades of adenocarcinoma tissues, different stages of tumor invasiveness, and lymph node status. Our research revealed distinctive expression patterns of CD70, VEGF, and CD90 across different stages and grades of colorectal cancer. our research signifies the potential clinical utility of the CD70, VEGF, and CD90 triad as prognostic markers in colorectal cancer. The combined analysis of these markers emerged as a potent prognostic tool, offering valuable insights into disease progression. Our research showed that epithelial CD90 is the most sensitive marker for both tumor stage and lymph node status. CD70 and VEGF showed a statistically significant relation with lymph node status only and not with tumor stage.

TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis.

Antibody-drug conjugates (ADCs) directed to trophoblast cell surface antigen 2 (TROP2) have gained approval as a therapeutic option for advanced triple-negative breast cancer, and TROP2 expression has been linked to unfavourable outcomes in various malignancies. In colorectal carcinoma (CRC), there is still a lack of comprehensive studies on its expression frequency and its prognostic implications in relation to the main clinicopathological parameters. We examined the expression of TROP2 in a large cohort of 1,052 CRC cases and correlated our findings with histopathological and molecular parameters, tumour stage, and patient outcomes. TROP2 was heterogeneously expressed in 214/1,052 CRCs (20.3%), with only a fraction of strongly positive tumours. TROP2 expression significantly correlated with an invasive histological phenotype (e.g. increased tumour budding/aggressive histopathological subtypes), advanced tumour stage, microsatellite stable tumours, and p53 alterations. While TROP2 expression was prognostic in univariable analyses of the overall cohort (e.g. for disease-free survival, p < 0.001), it exhibited distinct variations among important clinicopathological subgroups (e.g. right- versus left-sided CRC, microsatellite stable versus unstable CRC, Union for International Cancer Control [UICC] stages) and lost its significance in multivariable analyses that included stage and CRC histopathology. In summary, TROP2 is quite frequently expressed in CRC and associated with an aggressive histopathological phenotype and microsatellite stable tumours. Future clinical trials investigating anti-TROP2 ADCs should acknowledge the observed intratumoural heterogeneity, given that only a subset of TROP2-expressing CRC show strong positivity. The prognostic implications of TROP2 are complex and show substantial variations across crucial clinicopathological subgroups, thus indicating that TROP2 is a suboptimal parameter to predict patient prognosis.

The pathological and immunohistochemical profile of tumor angiogenesis in perforated sigmoid carcinoma–Case report and short literature review

&lt;b&gt;Background:&lt;/b&gt; Little is known about the physiopathological factors or mechanisms that underlie tumor invasion of the serosa and lead to perforation in the peritoneal cavity. The aim of the work was to analyze the pathological and immunohistochemical factors of tumor neoangiogenesis which could influence tumor perforation in colorectal cancer.&lt;br /&gt; &lt;b&gt;Results and discussions:&lt;/b&gt; 451 cases of complicated colorectal carcinomas were statistically analyzed, of which 19 cases were perforated sigmoid tumors. The immunohistochemical detection of mutant p53 proteins was the first molecular parameter examined in the context of the search for markers predicting the natural evolution mode in colorectal carcinomas.&lt;br /&gt; &lt;b&gt;Conclusions&lt;/b&gt;: Both loss of p53 and overexpression of bcl-2 proteins confer immortalization on cancer cells by inhibiting the processes leading to apoptosis. The paper proposes a review of the specialized literature, but also the presentation of a clinical case.

Estimation of relationship between serum lipids level and colorectal carcinoma: a cross-sectional study in VIMSAR, Odisha

The fourth most prevalent cancer-related cause of death worldwide is colorectal cancer. Some authors have suggested that among other risk factors, the serum lipid profile is one of the etiological risk factors. Therefore, measurement of serum lipid in this illness can establish a relationship between a healthy diet and colorectal cancer.To thoroughly research the connection between blood lipid levels and colon cancer outcomes in an effort to discover any tips for preventing this deadly condition.Patients who were hospitalised to the General Surgery department at VIMSAR, Burla between December 2020 and October 2022 were divided into two groups for the research. 40 instances of patients with colorectal cancer were randomly chosen as the case group, and 40 cases of patients with other diseases—diseases other than colorectal cancer—were chosen as the controls group. The cases were all diagnosed with carcinoma of various regions of the colon and rectum at various stages and in various age groups. Both the case and control groups' blood concentrations of TC, HDL-C, VLDL-C, LDL-C, and TG were determined for comparison and analysis.Regardless of sex, location, or stage of the malignancy, the blood levels of TC, TG, and LDL-C were lower in the tumour group than they were in the control group. On site comparison, right sided cases were much less common than left sided carcinomas, and the drop in the level of serum TC was statistically significant. However, significant differences were detected in the serum levels of the aforementioned parameters in advanced cases, which only included Dukes' C1 and C2. A negative relationship exists between serum TC, TG, and LDL-C levels and colorectal cancer. In order to design a more curative course of action for treating this dreadful illness, it may be used for follow-up treatment of colorectal carcinoma cases as well as a low level of these serum parameters preceding the disease or in early tumours. Our study only included a small number of people, thus more research and a cohort study based on the entire population are needed to fully understand this association.

Differences in Clinicopathological Features, P16Ink4a and P57KIP2 Immunohistochemical Expressions, and Survival Between Colorectal Carcinoma in Rectosigmoid and Other Colonic Locations.

Background One unique criterion of colorectal carcinoma (CRC) is the different locations within the colorectum. Different CRC sidedness/locationscould have distinct criteria, including risk factors, morphological features, genetic alterations, prognostic factors, and clinical outcomes. Nearly half of the CRC cases occur in the rectal-sigmoid locations, while other colonic locations constitute the other half. Investigating specific protein expression patterns in the rectosigmoid CRC (rsCRC) compared to other colonic (ocCRC) locations helps understand the disease pathogenesis, predict prognosis, and design personalized treatments. This study is the first to compare P16Ink4a and P57KIP2 immunohistochemical (IHC) expression in rsCRC to ocCRC and examine their relationship to disease outcomes in both locations. Materials and methods A comparative cross-sectional study used tissue microarray slides from rsCRC and ocCRC that were immunohistochemically stained by anti-P16Ink4a and P57KIP2 antibodies. A semi-quantitative scoring system classified each marker's expression as positive or negative. The statistical analysis compared clinicopathological features, P16Ink4a and P57KIP2 expressions, and their relationship to clinical outcomes in rsCRC and ocCRC cases. Results One hundred fifty CRCs were distributed into the rsCRC cases (n=86, 57.3%) and the ocCRC cases (n=64, 42.7%). The rsCRC cases had a significantly lower age <40 years (P=0.002), higher frequency of mismatch repair (MMR) proficientstatus (P=0.003), andperineural invasion (P=0.008), with lower disease-free (DFS) and overall survival (OS)(P=0.03, and P=0.015, respectively). Significantly higher positive P16Ink4a and P57KIP2 IHC expressions were found in the rsCRCs compared to the ocCRCs (P=0.02, and P=0.03, respectively); however, their relationship to the hazards (HR) of recurrence (HR=4.02, P=0.058, and HR=0.36, P=0.14, respectively) and mortality (HR=2.56, P=0.21, and HR=0.23, P=0.58, respectively)in the rsCRC group was statistically nonsignificant. In the ocCRC group, P16Ink4a positivity was significantly associated with a higher disease recurrence and mortality hazard (HR=8.19, P=0.007, and HR=5.57, P=0.037, respectively), while P57KIP2 positivity was significantly associated with a lower mortality hazard (HR=0.12, P=0.027). Conclusion The rsCRCs differ from ocCRCs in clinicopathological criteria and protein expression patterns. Though P16Ink4a and P57KIP2 IHC expressions are higher in the rsCRC than in the ocCRC, their value as outcome predictors is higher in the ocCRCs rather than the rsCRCs. P16Ink4a and P57KIP2 can act as prognostic markers and be suitable targets for therapy modulation in the ocCRC group.

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.