Cases Of Colorectal Carcinoma Research Articles

Mucin phenotypes and clinicopathological features of colorectal adenocarcinomas: Correlation with colorectal adenocarcinoma with enteroblastic differentiation

BackgroundThe mucin phenotypes of colorectal carcinoma (CRC) is related to the biological behavior and prognosis. But there has been no studies evaluating phenotypic characteristics in a large number of cases. Furthermore, colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of CRC and having poor prognosis. The aims of this study were to clarify the correlation between mucin phenotypes and tumor development, including biological behavior in CRC, as well as to investigate characteristic of mucin phenotypes in CAED. Methods and results974 CRC cases and 42 CAED cases of CRCs were classified five types (large-intestinal, small-intestinal, gastric, mixed, and unclassified) of mucin phenotypes by using immunohistochemistry (IHC). IHC was performed on tissue microarrays with antibodies against followings: MUC2, MUC5AC, MUC6, and CD10. In CRCs, large-intestine type has a relatively better prognosis, small-intestinal type frequently shows venous invasions, and liver metastases, gastric type has more high-histological grades and lymphatic invasions, mixed type shows originating from the right side of the colon, larger tumor size and mucinous type, but less venous invasions and liver metastasis, whereas the unclassified type showed poorer prognosis in overall survival with statistical significance. The majority of CAED were found to be small-intestinal type or unclassified type. ConclusionsThe phenotypic classification is useful for predicting the prognosis of CRCs. Small-intestinal type and unclassified type showed dismal prognosis in CRCs. We speculate that CAED having aggressive behavior and poor prognosis might reflect characteristics of small-intestinal and unclassified types.

Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Colorectal Carcinoma: A Potential Area of Focus for Future Diagnostics.

ObjectiveIn this study, we aimed to explore the potential diagnostic utility of human epidermal growth factor receptor 2 (HER2) expression in colorectal carcinoma. We investigated the association of HER2 expression with the type and grade of the tumor along with the pattern, staining intensity, and the percentage of cells stained.MethodsThis was an observational study involving 50 cases of colorectal carcinoma that underwent immunohistochemistry to analyze the HER2 expression.ResultsThe positive expression of HER2 was seen in 16 (32%) cases. The majority of the study population was between the fifth-seventh decades of life. The most commonly diagnosed tumor was conventional adenocarcinoma with grade II, cytoplasmic pattern, +2 positivity, and moderate intensity. The maximum positivity for HER2 was seen in tumors of the rectum in eight (16%) cases.ConclusionA substantial rate of HER2 overexpression paves the way for it to become a potential future target in cancer therapeutics.

Frequency and Clinicopathological Characteristics of Patients With KRAS/BRAF Double-Mutant Colorectal Cancer: An In Silico Study.

KRAS and BRAF mutations are currently thought to be mutually exclusive as their co-occurrence is extremely rare. Therefore, clinicopathological and molecular characteristics of colorectal carcinoma with KRAS/BRAF double mutations are unclear. We aimed to investigate the frequency and clinicopathological characteristics of double-mutant colorectal carcinoma and its differences from KRAS/BRAF single-mutant colorectal carcinoma using bioinformatics tools. We estimated the KRAS/BRAF double mutation frequency in the whole exon and coding sequences via bioinformatic analyses of three datasets from cBioPortal. We compared the clinicopathological characteristics, microsatellite instability status, BRAF classification, and tumor mutation burden of patients harboring the double mutants with those of patients harboring KRAS or BRAF single mutations. We integrated three large datasets and found that the frequency of the KRAS/BRAF double mutation in the dataset was 1.2% (29/2347). The double mutation occurred more frequently in males, with a slightly higher occurrence in the right side of the colon. Sex, histological type, histological grade, microsatellite instability, and tumor mutation burden of the patients harboring KRAS-mutant, BRAF-mutant, and double-mutant colorectal carcinoma varied significantly. The frequency of double-mutant colorectal carcinoma was 60 times higher than that previously reported. Significantly fewer double-mutant colorectal carcinoma cases were classified as BRAF class 1 and more were classified as unknown. Our findings indicate that the biological characteristics of double-mutant tumors are different from those of single-mutant tumors.

Spatial Organization and Prognostic Significance of NK and NKT-like Cells via Multimarker Analysis of the Colorectal Cancer Microenvironment.

Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3-), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1-CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (P trend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (P trend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (P trend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3-GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.

Tumor budding as a prognostic indicator in colorectal carcinoma: a retrospective study of primary colorectal carcinoma cases in a tertiary care center.

Colorectal carcinoma (CRC) is the third most common cancer worldwide. Along with many established prognostic factors, tumor budding is emerging as a valuable marker of prognosis. Tumor budding is not yet universally reported but it has recently been suggested in guidelines by ITBCC (International Tumor Budding Consensus Conference). Our aim is to study prognostic implications of tumor budding in CRC. Hundred cases of primary CRC specimens were retrospectively studied from January, 2016, to February, 2017. Tumor bud count and other histopathological parameters were evaluated from hematoxyline and eosin (H & E) stained slides. Survival analysis was done using Cox proportional hazards model. Association of tumor budding and cancer-specific survival was found to be statistically significant (P = 0.018 for average tumor budding and P = 0.035 for highest tumor budding) Tumor budding was found to be significantly associated with other clinicopathological parameters such as T stage, N stage, TNM stage, and lymphovascular invasion with p value < 0.05. Tumor budding is a valuable prognostic indictor for primary CRC and also significantly associated with other prognostic parameters. It should be reported routinely as a guide to prognosis and further management of patients.

FREQUENCY OF INCREASED PLASMA C-PEPTIDE LEVELS IN COLORECTAL CANCER PATIENTS

Objective: To assess the increased frequency of serum C-peptide levels in patients of colorectal carcinoma.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from Jul 2018 to Jan 2019.&#x0D; Methodology: A total of 100 cases of colorectal carcinoma were enrolled. Blood samples were obtained to assess C-peptide level. The C-peptide serum concentrations were deliberate through the Cobas 6000 by using the electro-chemi-luminescence immunoassay (ECLIA) method. If level of C-peptide was &gt;2 pmol/mL, then it was noted.&#x0D; Results: The mean age of all patients was 58.3 ± 5.4 years. There was a total of 136 (68%) females and 64 (32%) were males. The mean BMI of patients was 28.96 ± 12.31 kg/m2. The family history of colorectal carcinoma was positive in 6 (6%) cases. The mean C-peptide level was 4.55 ± 2.37 pmol/L. There were 33 (33%) patients with raised C-peptide level while 67 (67%) had normal c-peptide level.&#x0D; Conclusion: It is concluded that increased C-peptide level is high in patients with colorectal cancer.

Molecular and genetic features of colorectal carcinoma: pathomorphological demonstration of clinical cases and literature review

Background. Colorectal carcinoma (CRC) is one of the most widespread malignancies worldwide; its morbidity rate is on the third place amidst the most common cancers. According to present data, such molecular markers as CyD1, HIF1α, LC3B, p21, p53 as well as the detection of KRAS gene amplification could be used for evaluation of tumor grade, its invasiveness, risk of metastases, sensitivity to anti-EGFR treatment, and further prognosis for patient’s survive. Objective. The purpose of this study was to make a literature review of the CRC molecular diagnostic approaches and demonstrate 5 cases of colorectal carcinoma in patients of Dnipro-city region in purpose to reveal their molecular-genetic features. Methods. Five formalin fixed paraffin embedded specimens of colorectal carcinoma from patients of Dnipro-city region were evaluated pathomorphologically with histological, immunohistochemical and fluorescence in situ hybridization methods. Results. Case study revealed increased level of p53, p21, and LC3B expression, minor elevation of CyD1 and HIF1α expression in demonstrated samples. Amplification of KRAS gene was not found. Conclusion. Our data analysis had revealed multiple studies dedicated to CRC molecular diagnostics with controversial results, what could be explained by both variable methodological approaches and epidemiological peculiarities of CRC in different sites of the globe. Therefore, there is a necessity in empirical identification of the molecular-genetic features of colorectal carcinomas in patients of our region that could improve current state of the art in CRC diagnostic and treatment approaches. Achieved data are the result of the trial and our research of this issue is ongoing.

A Study on the Clinicopathological Profile of the Cases of Colorectal Carcinoma

Aim: To assess the clinicopathological details of patients with colorectal cancer in a tertiary care centre in India and compare it other studies reported in the literature.&#x0D; Study Design: This is a retrospective study conducted on all the patients who were admitted in the period of 2017 to 2020.&#x0D; Place and Duration of Study: Department of Pathology, Saveetha Medical College, Thandalam, Chennai. The data was processed and the manuscript was prepared between June 2020 and January 2021.&#x0D; Methodology: Patient details were collected from the histopathology records and the parameters studied were age, gender, tumour site, histological type, differentiation and tumour stage of the colorectal carcinoma. The sampling was done using the complete enumerate sampling method. The patients diagnosed histopathologically as colorectal carcinoma were included in our study.&#x0D; Results: A total of 51 patients had been admitted in the years 2017, 2018, and 2019 in our institute. There was a female predominance among the patients. The mean age of the patients was lesser than the mean age of colorectal cancer cases in other studies which have been reported in the country. The most common tumour site was rectum in both the sexes and the most common histologic type was adenocarcinoma. The most common histological differentiation was moderate differentiation.&#x0D; Conclusion: The increased incidence in younger patients as compared to previous studies may be attributable to the lifestyle and dietary changes.

Status of microsatellite instability in different histomorphological patterns of colorectal carcinoma among a group of Bangladeshi people

Background: This cross- sectional observational study was carried out with an aim to look for microsatellite instability (MSI) status in colorectal carcinoma and their association with different histomorphological patterns and biological behavior of colorectal carcinoma.Methods: This cross-sectional observational study was done in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University Hospital (BSMMU), Dhaka, Bangladesh during September 2014 to October 2015. A total of 39 surgically resected sample of colorectal carcinoma were included. Consent from each patient was taken. The samples were histopathologically evaluated according to the standard protocol. The statistical analyses were done using Statistical packages for social sciences (SPSS 15) for Windows.Results: A total of 39 cases of colorectal carcinoma were included in this study. Majority of the patients (55.5%) was in 6th decade in MSI and 29.1% were MSI absent group. The mean age was found 47.67±10.97 years in present group and 47.84±14.26 years in absent group. The difference was not statistically significant (p&gt;0.05). TNM stage with MSI was observed. The mean CEA level was 100.74±103.66 and 60.43±91.72. The mean Hb was 9.72±1.99 % and 9.92±2.17, the range was 7.2-12.2 and 4.6-13.4 among the groups. The mean difference was not statistically significant (p&gt;0.05). Ulcerated was 3 (33.3%) and 19 (64.5%). Stage 3 tumor was 4 (44.4%) and 16 (51.6%). Grade 2 tumor was 5 (55.6%) and 17 (58.0%).Conclusions: For the first time in Bangladesh, this study was undertaken to evaluate the microsatellite instability (MSI) status in colorectal cancer tissue and their association with different histomorphological patterns of colorectal carcinoma.

Clinicopathologic characteristics of FBXW7-mutated colorectal adenocarcinoma and association with aberrant beta-catenin localization

Oncogenic mutations in the adenomatous polyposis coli (APC)/Wnt signaling pathway are well documented. The FBXW7 gene (F-box and WD repeat domain-containing 7) encodes a member of the ubiquitin-proteasome complex that is more recently described to antagonize the oncogenic Wnt pathway by promoting the degradation of β-catenin encoded by the CTNNB1 gene. The pathologic significance of FBXW7 mutation in colorectal carcinoma (CRC) remains under-reported. In this study, we report the clinicopathologic and β-catenin immunohistochemical features of a single-institution cohort (83 cases) of FBXW7-mutated CRC compared with CTNNB1-mutated CRC. FBXW7-mutated CRC was more common in older patients (p=0.031) and in the left/distal colon (p=0.022). Immunohistochemical analysis revealed that aberrant nuclear/cytoplasmic β-catenin localization was identified in a significantly high proportion of FBXW7-mutated CRCs. When compared with CTNNB1-mutated CRC, FBXW7-mutated CRC showed a significantly higher proportion of microsatellite instability-stable tumors with intact expression of DNA mismatch repair proteins and had significantly more frequent co-occurrence of missense TP53 and KRAS mutations. The most frequently mutated FBXW7 residues/hotspots were located within the WD repeat domains (aa 378-659), which were also associated with aberrant nuclear/cytoplasmic localization of β-catenin protein. Our results indicate the unique pathologic characteristics of FBXW7-mutated CRC with frequent co-occurrence of missense mutant TP53and KRAS. The mutated FBXW7 residues/hotspots and its association with aberrant nuclear/cytoplasmic β-catenin localization further support the oncogenic role of FBXW7 in colon carcinogenesis.

English

BACKGROUND Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity from cancer. The risk group ranges from 69-79 years and the mean age being 62 years. This study was done to assess and compare the clinicopathological characteristics of colorectal carcinoma in adults above and below 50 years and also study the expression of MLH1 for demonstration of microsatellite instability in colorectal carcinoma. METHODS This was a cross-sectional study conducted in the Government Medical College, Trivandrum, Kerala, after obtaining ethical committee clearance (IEC.15/18/2017/MCT dt 19/12/2017). All cases of colorectal carcinomas that had surgical resection and the specimen brought to the Pathology department were included in the study. Carcinomas which were secondary deposits from elsewhere were excluded. Sample size was 61 calculated using the formula n=4pq/d2. Study variables included age, site, histology type, stage, differentiation, lymphatic and vascular spread and lymphocyte infiltration were recorded. Routine H&amp;E sections were used to observe the morphology, invasion, grade, and stage of the tumours. Then MSI was detected using MLH I. Clinical details were collected from the patients and medical records. Data were entered in excel sheets. categorical variables are expressed as proportions and quantitative variables are expressed as mean and standard deviation. Chi square test was used as the test of significance for categorical variables. RESULTS Clinicopathological features of 61 cases were studied and the mean age was 61 years. Most cases were left-sided cancer with moderately differentiated classical adenocarcinoma being the most common histopathological subtype. Individuals less than 50 years presented with adenocarcinoma with mucinous and signet ring cell morphology and with poor differentiation. 67.2 % had no lymphovascular invasion. The majority of the cases were positive for MLH1. The cases which showed negativity for MLH1 were cases with mucinous differentiation or signet ring cell type and were predominantly moderate to poorly differentiated and this relation was found to be significant. CONCLUSIONS The study concludes that the majority of CRC occurred in individuals between 61 - 70 years of age, they were left-sided moderately differentiated adenocarcinomas with stage IIB disease, most were negative for lymphovascular invasion and tumour infiltrating lymphocytes. Younger patients had a higher percentage of mucinous and signet-ring cell histology. 78.7 % were positive for MLH1. KEY WORDS Colorectal carcinoma, MLH1, Microsatellite instability

Immunohistochemical Expression of “HCG-β” in Colorectal Carcinoma

BACKGROUND: Tumor budding is associated with adverse histology and is a predictor of lymph node metastasis. Human chorionic gonadotropin-beta (hCG-β) expression in non-trophoblastic tumors has been associated with aggressive behavior. AIM: Evaluation of tumor budding and hCG-β _immunohistochemical expression in colorectal carcinoma (CRC), and correlation of their expression with various clinicopathological parameters. MATERIALS AND METHODS: Immunohistochemical staining for hCG-β _was performed on paraffin-embedded sections of 60 cases of CRC. Tumors with cytoplasmic or membranous staining of more than five epithelial cell clusters were designated hCG-β _positive; otherwise, they were designated hCG-β _negative. Tumor budding was assessed in hematoxylin and eosin stained slides and was classified as; low: 0–4 buds, intermediate: 5–9 buds and high: ≥10 buds; with exclusion of pure mucoid or signet ring cell morphology cases from analysis. RESULTS: Tumor budding was low in (58.8%) of the cases, intermediate in (15.7%), and high in (25.5%). There was a statistically significant correlation between tumor budding and tumor histological grade (p = 0.011), lymph node metastasis (N) (p = 0.009), overall pathologic stage group (p = 0.009), modified Dukes’ stage (p = 0.009), lymphovascular invasion (p = 0.000), and desmoplastic reaction (p = 0.004). Positive hCG-β _alpha expression was detected in 12 (20%) of cases. There were statistically significant correlations between hCG-β _expression and each of lymphovascular invasion (p = 0.042) and tumor budding (p = 0.000). CONCLUSION: hCG-β _is a marker of aggressiveness that may have essential role in tumor invasion. Tumor budding is crucial event in tumor invasion and metastasis. Tumor budding with hCG-β _expression is a novel prognostic parameter and may represent a potential therapeutic target.

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas.

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - (GBd) and poorly differentiated clusters - (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timişoara. CRC cases were classified based on hematoxylin-eosin slides, using the conventional grading system, GBd, and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently, we evaluated associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t) most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005), and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC. Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.

A STUDY OF HISTOPATHOLOGICAL DISTRIBUTION IN COLORECTAL CANCER

Despite of advances in surgical techniques and adjuvant chemotherapeutic regimens, colorectal cancer remains one of the major leading causes of deaths worldwide. Histopathology is an important factor in the treatment and prognosis of cancer. The purpose of this study was to describe the different histopathological pattern in colorectal cancer. 81 cases of colorectal carcinoma received in pathology department over a period of four years were included in the study. The surgical specimen and colonoscopic biopsies' gross features were noted and samples were stained with Haematoxylin and Eosin. Detailed microscopic examination of tumor with lymph node status was done followed by histological typing. Grading of the tumor, age and sex distribution of cases were also noted. The commonest histopathological nding was adenocarcinoma 75.32% followed by mucinous adenocarcinoma 9.88% and signet ring cell carcinoma 8.64%. Among 61 cases of adenocarcinoma most commonly moderately differentiated adenocarcinoma 60.66% was noted.

Mismatch Repair Protein Expressions in Cohort of Colorectal Carcinoma Patients in Lagos.

Colorectal carcinoma (CRC) is a major cause of morbidity and mortality worldwide. Microsatellite instability pathway is important in the pathogenesis of CRC. Immunohistochemistry expression of mismatch repair (MMR) proteins serves as surrogate marker for MMR gene mutation. This study aimed to determine MSI status of a cohort of CRC cases using immunohistochemistry. Surgical pathology blocks of resected colonic carcinoma (CC) between 2011 and 2015 were extracted from our departmental archives and The Specialist Laboratories in Lagos. Immunohistochemical expression profile of 4 MMR proteins was assessed in the representative blocks and this was correlated with the demographic and pathological characteristics. There were 19 males and 16 females with CC, mean age of 51.6 years, and 40% of them were below 50 years of age. Twenty (57.1%) out of the 35 CC cases seen were mismatch repair proficient (pMMR) while the remaining 15 (42.9%) were mismatch repair deficient (dMMR). Seven dMMR cases were seen equally on the right and left colonic tumors respectively. Five (71.4%) out of the 7 mucinous tumors in this study were dMMR, right sided with 3 of them in patients who were below 50 years of age. The frequency of mismatch repair deficiency in CC among Nigerians is high, and presence of right-sided mucinous colon cancer in patients below 50 years is highly suggestive of dMMR status. Mutation studies of larger patient samples to determine the percentage with germline mutation will further our knowledge, and influence therapeutic options for CC.

Ki67 Protein expression and correlation with the histological grade and pTNM stage of colorectal carcinoma

: Colorectal cancer, is third most frequently encountered malignancy worldwide. Histological grade, stage, and proliferative index act as vital prognostic markers, playing a decisive role in patient care and prognosis. While histopathological examination can determine grade and stage, Ki67 protein expression by immunohistochemistry represents the proliferative capacity of the malignant cell population. : This Study was conducted to immunohistochemically analyze expression of Ki67 protein and its change with respect to different grades and stage of colorectal adenocarcinoma. : A total of 66 histologically diagnosed cases of colorectal carcinoma underwent histopathological examination followed by immunohistochemistry for Ki67 protein. : A statistically significant (p=0.04) correlation was obtained between Ki67 labelling index and histopathological grade, with higher values of Ki67 labelling index in poorly differentiated carcinomas (43.2±1.7). The Ki67 labelling index value was lowest in stage IV disease (11.4±2.4) with metastatic burden, with higher values in lower stage diseases, however this correlation was not found to be significant statistically (p=0.07). : The rate of cell division and proliferation measured by Ki-67 antibody is related to histological grade of the malignancy, demonstrating higher mitotic activity with loss of differentiation and anaplasia. Stage IV disease have lower mitotic activity, thus may be less amenable to cytostatic chemotherapy drugs, and require multimodality treatment with addition of radiotherapy and other drug regimes.

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans.

BackgroundEmerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to contribute to existing understanding of these lesions.Methods and findingsFormalin-fixed paraffin-embedded CRC colectomy tissues and their corresponding non-tumour margins of resected tissues were sectioned and stained with COX-2 antibody. Adenomatous polyp tissues from non-cancer bearing individuals were similarly processed for comparison. COX-2 expression was scored for percentage (< 5% = 0; 6%-25% = 1; 26%-50% = 2; 51%-75% = 3; 76%-100% = 4) and intensity (no staining = 0; yellow = 2; yellowish-brown = 3, brown = 4). Total immunoscore (percentage + intensity score) ≥ 2 was regarded as positive COX-2 expression. Outcome was statistically evaluated with clinicopathological data to determine COX-2 expression-associated and predictor variables. Ninety-five CRC cases and 27 matched non-tumour tissues as well as 31 adenomatous polyps met the inclusion criteria. Individuals with CRC had a mean age of 56.1 ± 12.6 years while those with adenomatous polyps had a median age of 65 years (range 43–88). COX-2 was differentially overexpressed in CRCs (69/95; 72.6%) and in adenomatous polyps (17/31; 54.8%) than in non-tumour tissues 5/27 (18.5%); p < 0.001). The difference in COX-2 expression between CRC and polyps was non-significant (p > 0.065). Tumour grade, advanced pT-stage, tumour-infiltrating lymphocytes, and dirty necrosis were also significantly associated with COX-2 expression (p < 0.035; 0.043, 0.035 and 0.004, respectively). Only dirty necrosis and Crohns-like lymphocytic aggregates predicted COX-2 expression (p < 0.05).ConclusionThis study showed a progressive increase in COX-2 expression from normal to adenomatous polyp and CRC tissues, this being associated with poorer prognostic indicators. Although COX-2 appears early in CRC, it may play a secondary role in promoting tumour growth and invasiveness.

Clinicopathological significance of neutrophil-rich colorectal carcinoma

AimsThe importance of the interaction between tumour cells and neutrophils has recently begun to emerge. However, the significance of tumour-infiltrating neutrophil (TIN) in colorectal carcinomas (CRCs) remains unclear. The aim...

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma.

Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2). Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors, 62.0% were positive for KRAS protein expression and there was a higher percentage of KRAS-positive tumor cells and a higher intensity of immunohistochemical reaction in T2 than in T1 samples. This could not be attributed to differences in KRAS mRNA levels, suggesting regulation via miR-544a-3p expression which was significantly decreased in T2 samples. Furthermore, we demonstrated that tumor samples carrying the KRAS-LCS6 variant allele had significantly higher protein expression of the wild-type KRAS. Our results suggest the role of the KRAS-LCS6 polymorphism and miR-544a-3p expression in the regulation of wild-type KRAS protein expression in sporadic CRC.