Mesothelin expression and its prognostic role according to microsatellite instability status in colorectal adenocarcinoma

Kim, Hyunsung; Chung, Yun Jae; Paik, Seung Sam; Jang, Kiseok; Shin, Su‐Jin

doi:10.1097/md.0000000000016207

Cited by 3 publications

(5 citation statements)

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“…In contrast, the present study used MN-1 antibody, which has a higher affinity and positivity (% positive cells in immunohistochemistry) than 5B2 (11,24). Kim et al reported the prognostic role of MSLN in microsatellite unstable CRCs using SP74 antibody (17); however, this type of association was not confirmed in our cohort (data not shown). The discrepancies in these studies might result from the patient cohort (patient number and pathological stage) as well as the anti-MSLN antibody used.…”

Section: Msln Expression --------------------------------------------contrasting

confidence: 64%

“…The present study analyzed the impact of diffuse MSLN expression on the survival of stage II to IV CRC patients and determined its expression as a potential independent risk factor (HR, 2.26; 95% CI, 1.04-4.91; P= 0.039). Several studies have analyzed the impact of tumor MSLN expression on the survival of CRC patients (15)(16)(17). Shiraishi et al (15) found an adverse impact of MSLN expression on the survival of stage II/III CRC patients with statistical significance; however, Kawamata et al (16), found no significant difference in stage I to IV patients.…”

Section: Msln Expression --------------------------------------------mentioning

confidence: 99%

“…In colorectal carcinomas, the clinicopathological profiles and prognosis of MSLN-positive CRC patients have not been fully studied. Furthermore, the biological significance of MSLN expression in CRC development remains to be elucidated (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

et al. 2020

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Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN therapy. In vitro experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P= 0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04-4.91; P= 0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting metastasis could be targeted by anti-MSLN therapies.

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Section: Msln Expression --------------------------------------------contrasting

confidence: 64%

Section: Msln Expression --------------------------------------------mentioning

confidence: 99%

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Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

et al. 2020

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“…Membrane MSLN staining was performed by a trained pathologist. The staining intensity for evaluating MSLN protein expression was recorded using a four-tiered scoring system (0: no detectable signal, 1 + : weak, 2 + : moderate, and 3 + : strong), which is described in the antibody kit's instructions and previous reports using the same clone of the anti-MSLN antibody [ 18 – 20 ]. In addition, we used a quantitative analysis of IHC (H-Score) for a more detailed evaluation of the expression status.…”

Section: Methodsmentioning

confidence: 99%

High mesothelin expression is correlated with non-squamous cell histology and poor survival in cervical cancer: a retrospective study

et al. 2022

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Background Mesothelin (MSLN) is a cell-surface glycoprotein found in various solid tumours. Cancer therapies targeting MSLN have been developed in recent years; however, the available information on MSLN expression in cervical cancer is limited. This study aimed to evaluate MSLN expression in various histological types of cervical cancer and examine its relationship with prognosis. Methods This retrospective study included patients with cervical cancer who underwent primary surgery between January 2000 and December 2020 at our institution. MSLN expression was evaluated by immunohistochemistry using clone SP74 and defined as positive if MSLN was expressed at any intensity. High MSLN expression was defined as an intensity of ≥ 2 + in ≥ 30% of tumour cells. The association between MSLN expression and clinicopathological factors was evaluated. Results Overall, 123 patients were identified, and 140 tumour samples, including 17 paired primary and metastatic samples, were evaluated. Concerning histological type, 67 patients had squamous cell carcinoma (SCC), whereas 56 had non-SCC. MSLN expression was observed in 98.4% (121/123) of primary tumours. High MSLN expression was observed in 63.4% of samples (78/123), but it differed between the histological types (49.2% for SCC vs. 80.4% for non-SCC, p < 0.001). There was a significant correlation between MSLN expression in primary and metastatic lesions (Rs = 0.557, p = 0.015). In patients with common histological types, overall survival (OS) was shorter in the high MSLN expression group than in the low MSLN expression group (hazard ratio, 3.53; 95% confidence interval, 1.16–15.3, p = 0.03). Conclusions MSLN was highly expressed in patients with cervical cancer, especially in those with non-SCC. High MSLN expression in the primary lesion was significantly associated with poor OS, and its expression was maintained in metastatic lesions. Our findings indicate that MSLN may be an attractive therapeutic target for cervical cancer. Trial registration Retrospectively registered. 2014-393. 1 June 2015

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“…Microsatellites are short tandem repeats that are found throughout the human genome [ 39 ]. Compared with normal tissue, the microsatellite of tumor tissue changes the length of the microsatellite due to the insertion or deletion of repeating units, called microsatellite instability (MSI) [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA

Chen

Shi

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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Background. Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. Methods. DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). Results. In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs ∗ 15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA. Conclusions. The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs ∗ 15) mutation may be associated with SSA in this patient.

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Mesothelin expression and its prognostic role according to microsatellite instability status in colorectal adenocarcinoma

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 30 publications

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

High mesothelin expression is correlated with non-squamous cell histology and poor survival in cervical cancer: a retrospective study

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA

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