Clinical significance of mucinous component in colorectal adenocarcinoma: a propensity score-matched study

Background This study aims to investigate the clinical significance and prognostic value of mucinous component (MC) in colorectal adenocarcinoma (AC). Methods Patients with colorectal AC and AC with MC (ACMC) (1–100%) underwent surgical resection between January 2007 and February 2018 were retrospectively reviewed. Propensity score matching (PSM) was performed according to a 1:1 ratio. Receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off value of MC ratio for prognostic prediction. The clinicopathological features and 3-year overall survival (OS) of AC patients, mucinous adenocarcinoma (MAC) (MC > 50%) patients, and ACMC (1–50%) patients were compared before and after matching. Multivariable analysis was used for analyzing independent risk factors related to prognosis. Results A total of 532 patients were enrolled in this study. Patients with AC, MAC, and ACMC (1–50%) exhibited different clinicopathological features. However, their 3-year OS rates were similar (82.00% vs. 74.11% vs. 81.48%, P = 0.38). After matching, ROC curve determined 70% as the optimal cut-off value. And patients with ACMC > 70% had a much poorer 3-year OS compared with ACMC (1–70%) patients and AC patients (47.37% vs. 86.15% vs. 79.76%, P < 0.001). In addition, ACMC > 70% was revealed as a risk factor for poor survival in univariate analysis (HR = 1.643, 95%CI = 1.025–2.635, P = 0.039), though not an independent risk factor in multivariable analysis (HR = 1.550, 95%CI = 0.958–2.507, P = 0.074). Conclusions MAC is usually diagnosed at an advanced stage. MAC has a similar survival with AC and ACMC (1–50%) patients before and after matching. Patients with ACMC > 70% exhibited a much poorer OS, and should be given more clinical attention.

Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer

Background and objectives: The present study aimed to evaluate the clinicopathological significance and prognostic implications of REG4 immunohistochemical expression in colorectal cancer (CRC). Materials and Methods: We performed immunohistochemical analysis for REG4 cytoplasmic expression in 266 human CRC tissues. Correlations between REG4 expression, clinicopathological characteristics, and survival were investigated in CRC. Results: REG4 was expressed in 84 of 266 CRC tissues (31.6%). REG4 expression was significantly more frequent in the right colon than that in the left colon and rectum (p = 0.002). However, we observed no significant correlation between REG4 expression and other clinicopathological parameters. REG4 expression was significantly higher in CRCs with low stroma than in those with high stroma (p = 0.006). In addition, REG4 was more frequently expressed in CRCs with the mucinous component than in those without it (p < 0.001). There was no significant correlation between REG4 expression and overall recurrence-free survival (p = 0.132 and p = 0.480, respectively). Patients with REG4 expression showed worse overall and recurrence-free survival in the high-stroma subgroup (p = 0.001 and p = 0.017, respectively), but no such correlation was seen in the low stroma subgroup (p = 0.232 and p = 0.575, respectively). Conclusions: REG4 expression was significantly correlated with tumor location, amount of stroma, and mucinous component in CRCs. In patients with high stroma, REG4 expression was significantly correlated with poor overall and recurrence-free survival.

Mismatch Repair Deficiency in Colorectal Adenocarcinoma: Clinical, Pathological and Prognostic Features, a Single Center’s Experience of 1002 Cases

Background and Study Aims: Microsatellite instability pathway caused by loss of DNA “Mismatch Repair genes” (MMR) is responsible of Lynch Syndrome-related tumors and 10-15% of sporadical colorectal cancers. Although MSI-test is regarded as the golden standard for detection of “Lynch Syndrome-related tumors”, there are increasing evidence on similar analytic sensitivity of immunohistochemical evaluations. Patinets and Metods: We retrospectively evaluated 1002 colorectal tumors for loss of DNA MMR protein (MLH1, PMS2, MSH2, MSH6) immunohistochemically. The results were correlated with clinicopathological features and high level-microsatellite instability (MSI-H) related histological parameters. Results: MMR protein expression loss was observed in 9.8% of the cases. MLH1-PMS2 loss (53.2%) was the most common loss followed by MSH2-MSH6 (31.6%), isolated PMS2 loss (12%), and isolated MSH6 loss (2%). MMR deficiency was more frequent under 50 years-old (p<0.0001), in right colon tumors (p<0.0001), poorly differentiated tumors (p<0.0001), tumors with tumor infiltrating lymphocytes (p<0.0001), mucinous component (p=0.001), and medullary component (p<0.0001). Also MMR deficiency was less frequent in tumor with tumor budding (p<0.0001) and dirty necrosis (p<0.0001). The 5 years-survival rate was 55.7%. No significant correlation was found with MMR deficiency and survival. Conclusions: MMR deficiency was observed in 9.8% of the cases with distinct clinicopathological features. The results were consistent with previous studies. Unlike the literature, we did not find any statistically significant difference between MMR deficiency and prognosis.

Clinicopathological significance of WT1 expression in invasive breast carcinoma with >90% mucinous component

AimsThis study was aimed to investigate the clinicopathological significance of immunohistochemical (IHC) Wilm’s tumour 1 (WT1) expression in invasive breast carcinoma with >90% mucinous components.MethodsOne hundred specimens of invasive breast carcinoma with >90% mucinous component were collected. All H&E-stained slides were reviewed, and the clinicopathological data, including sex, age, tumour size, nuclear grade, histological grade, growth pattern and lymph node (LN) status, were collected. IHC staining of WT1, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 was performed. Fluorescence in situ hybridisation was used to verify the amplification of the HER2 gene. The relationship between WT1 expression and clinicopathological features was analysed statistically.ResultsWT1 expression was detected in 67% (67/100) of invasive breast carcinoma with >90% mucinous components. WT1 expression was significantly associated with low-to-intermediate nuclear grade/histological grade, ER and PR positivity, HER2 negativity, Ki-67 proliferation index <30% and noLN metastasis (all p<0.001). Micropapillary architecture was observed in 80% of cases. WT1 expression was not significantly correlated with different percentage of micropapillary components (p=0.422). None of the histological grade 3 tumours, tumours with HER2 overexpression/amplification and triple-negative specimens showed WT1 expression.ConclusionsWT1 expression was significantly related with low-intermediate nuclear/histological grade, ER positivity, HER2 negativity, a lower Ki-67 proliferation index and no LN metastasis in invasive breast carcinoma with >90% mucinous component. The micropapillary growth pattern in this type of tumour did not show a specific relationship with WT1 expression.

Colocolic Intussusception in an Adult Patient Secondary to Caecal Adenocarcinoma

Acute intestinal invagination is the pathology of infants and small children. Its occurrence in adults is rare, and it represents 1 to 5% of intestinal occlusions often leading to the discovery of an organic cause that may be tumor. We report the case of a 72-year-old patient admitted to the emergency room of Ibn Sina Rabat, Morocco, for intestinal occlusion. The abdominal CT scan showed a voluminous intestinal invagination on a very probable heterogeneous digestive mass. The treatment was an open right hemicolectomy. The histopathological examination of the surgical specimen concluded a colonic well-differentiated adenocarcinoma with a 30% mucinous component. By review of literature, we discuss diagnostic and therapeutic procedures in emergency.

Clinicopathological Significances of Tumor–Stroma Ratio (TSR) in Colorectal Cancers: Prognostic Implication of TSR Compared to Hypoxia-Inducible Factor-1α Expression and Microvessel Density

The present study aimed to elucidate the clinicopathological significance and prognostic implications of tumor–stroma ratio (TSR) in colorectal cancers (CRCs). TSRs were investigated in 266 human CRC specimens. The correlations between TSR and clinicopathological characteristics and survival were evaluated. The hypoxia-inducible factor-1α (HIF-1α) immunohistochemical expression of tumor cells and microvessel density (MVD) of stroma were compared between stroma-low and stroma-high subgroups. Results: Stroma-low was found in 185 of 266 CRCs (69.5%). Stroma-low was significantly correlated with less frequent vascular and perineural invasion and distant metastasis than stroma-high. HIF-1α of tumor cells was more highly expressed in the stroma-high subgroup than in the stroma-low subgroup. In addition, MVD was significantly higher in the stroma-high subgroup compared to the stroma-low subgroup. The stroma-low rate was increased considerably in CRCs with a mucinous component and decreased in CRCs with a micropapillary component. There were significant correlations between stroma-low and better overall and recurrence-free survivals. Similar to the literature, we observed that stroma-low was significantly correlated with favorable tumor behaviors and better survival. The microscopic examination of TSR can be useful for predicting the prognosis of CRC patients.

Deep learning quantified mucus-tumor ratio predicting survival of patients with colorectal cancer using whole-slide images

Background In colorectal cancer (CRC), mucinous adenocarcinoma differs from other adenocarcinomas in gene-phenotype, morphology, and prognosis. However, mucinous components are present in a large amount of adenocarcinoma, and the prognostic value of mucus proportion has not been investigated. Artificial intelligence provides a way to quantify mucus proportion on whole-slide images (WSIs) accurately. We aimed to quantify mucus proportion by deep learning and further investigate its prognostic value in two CRC patients cohorts. Methods Deep learning was used to segment WSIs stained with hematoxylin and eosin. Mucus-tumor ratio (MTR) was defined as the proportion of mucinous component in the tumor area. A training cohort (N = 419) and a validation cohort (N = 315) were used to evaluate the prognostic value of MTR. Survival analysis was performed by the Cox proportional hazard model. Result Patients were stratified to mucus-low and mucus-high groups by 24.1% as the threshold. In the training cohort, patients with mucus-high had unfavorable outcomes (hazard ratio for high vs. low 1.88, 95% confidence interval 1.18-2.99, P = 0.008), with 5-year overall survival rates of 54.8% and 73.7% in mucus-high and mucus-low groups, respectively. The results were confirmed in the validation cohort (2.09, 1.21-3.60, 0.008; 79.8% vs. 62.8%). The prognostic value of MTR was maintained in multivariate analysis for both cohorts. Conclusion The deep learning quantified MTR was an independent prognostic factor in CRC. With the advantages of advanced efficiency and high consistency, our method is suitable for clinical application and promotes precision medicine development.

Clinicopathological, molecular features and prognosis of colorectal cancer with mucinous component

Background: Colorectal cancer (CRC) with mucinous component is associated with distinct characteristics and controversial prognosis. Patients & methods: A total of 1800 CRC patients were retrospectively enrolled and grouped by the mucinous content of the primary tumors. The clinicopathological characteristics and overall survival rate were compared between groups. Results: Mucinous adenocarcinoma (MAC) and adenocarcinoma with mucinous component (AMC) had higher frequencies of DNA mismatch repair protein deficiency, KRAS, BRAF and PIK3CA mutations as compared to those of conventional adenocarcinoma (CAC). MAC had worse prognosis than CAC. However, MAC was not an independent prognostic factor in multivariable analysis. Conclusion: Molecular features of AMC and MAC were similar, which were different from those of CAC. Neither MAC nor AMC were independent prognostic factors for CRC.