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

Inoue, Satoshi; Tsunoda, Takumi; Riku, Miho; Ito, Hiroki; Inoko, Akihito; Murakami, Hideki; Ebi, Masahide; Ogasawara, Nagahisa; Pastan, Ira; Kasugai, Kunio; Kasai, Kenji; Ikeda, Hiroshi; Inaguma, Shingo

doi:10.3892/ol.2020.11290

Cited by 31 publications

(42 citation statements)

References 32 publications

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“…Our analysis of 1619 colorectal carcinomas identified significant associations with advanced pT stage and lymph node metastases. This is in line with data from 4 earlier studies all describing associations between high MSLN expression and parameters for cancer aggressiveness or poor patient prognosis [ 42 , 99 , 100 , 104 ]. However, the absence of statistical associations between MSLN expression and tumor phenotype and/or prognosis in carcinomas of the bladder, breast, ovary, endometrium, kidney, lung, and stomach argues against a major prognostic role of MSLN expression levels.…”

Section: Discussionsupporting

confidence: 92%

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

et al. 2021

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Mesothelin (MSLN) represents an attractive molecule for targeted cancer therapies. To identify tumors that might benefit from such therapies, tissue microarrays including 15,050 tumors from 122 different tumor types and 76 healthy organs were analyzed for MSLN expression by immunohistochemistry. Sixty-six (54%) tumor types showed at least occasional weak staining, including 50 (41%) tumor types with at least one strongly positive sample. Highest prevalence of MSLN positivity had ovarian carcinomas (serous 97%, clear cell 83%, endometrioid 77%, mucinous 71%, carcinosarcoma 65%), pancreatic adenocarcinoma (ductal 75%, ampullary 81%), endometrial carcinomas (clear cell 71%, serous 57%, carcinosarcoma 50%, endometrioid 45%), malignant mesothelioma (69%), and adenocarcinoma of the lung (55%). MSLN was rare in cancers of the breast (7% of 1138), kidney (7% of 807), thyroid gland (1% of 638), soft tissues (0.3% of 931), and prostate (0 of 481). High expression was linked to advanced pathological tumor (pT) stage (p < 0.0001) and metastasis (p < 0.0001) in 1619 colorectal adenocarcinomas, but unrelated to parameters of malignancy in 1072 breast-, 386 ovarian-, 174 lung-, 757 kidney-, 171 endometrial-, 373 gastric-, and 925 bladder carcinomas. In summary, numerous important cancer types with high-level MSLN expression might benefit from future anti-MSLN therapies, but MSLN’s prognostic relevance appears to be limited.

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Section: Discussionsupporting

confidence: 92%

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

et al. 2021

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“…The whole study has been carried out in compliance with the Helsinki Declaration. The source of 269 formalin‐fixed paraffin‐embedded (FFPE) samples of primary colorectal tumors was previously described 20,21 . Briefly, tumors resected at the Aichi Medical University Hospital from 2009 to 2012 were collected, along with patients' clinical information.…”

Section: Methodsmentioning

confidence: 99%

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

Koshino

Inoue

Sugimura-Nagata

et al. 2021

Pathology International

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Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers worldwide, with high morbidity and mortality rates. Despite numerous attempts to identify prognostic markers for the CRC patients, the significance of the association of cellular proliferation markers with survival is controversial. Here we used immunohistochemistry to detect four markers of cellular proliferation expressed in primary CRC tissue specimens (n = 269) to assess their potential to serve as prognostic factors. CRC cells variably expressed phospho-histone H3 (PHH3) (range, 0-76 per high-powered field (HPF); median, 7 per HPF), cyclin A (CCNA) (range, 11.3-73.7%; median, 32%), geminin (GMNN) (range, 7.8-82.0%; median, 37.1%), and marker of proliferation Ki-67 (MKI67) (range, 4.9-96.6%; median, 49.6%). Among them, patients with PHH3-high (≥7 per HPF) tumors uniquely experienced significantly longer 5-year survival than those with PHH3-low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047). Multivariable Cox hazards regression analysis identified PHH3-high (hazard ratio, 0.54; 95% confidence interval, 0.31-0.92; P = 0.025) as potential favorable factors. PHH3 levels inversely associated with pT stage (P < 0.0001) and were significantly and inversely associated with tumor diameter (ρ = −0.314, P < 0.0001). These findings support the use of PHH3 immunohistochemistry for predicting the prognoses of patients with CRC.

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“…Mesothelin expression and co-expression of mesothelin and CA125 were associated with tumor aggressiveness in several types of carcinomas [ 7 – 15 ]. In endometrial carcinoma, serous carcinoma, clear cell carcinoma, carcinosarcoma, and mixed carcinoma are more aggressive histological subtypes than grade 1 and 2 endometrioid carcinoma [ 22 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Only mesothelin expression was associated with worse prognosis in several carcinomas [ 7 – 9 , 12 – 15 ]. Moreover, co-expression was correlated with worse prognosis in pancreatic, ovarian, and endometrial serous carcinomas [ 10 , 11 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis

et al. 2021

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Background This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma. Methods Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined. Results Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p < 0.01). More patients with mesothelin expression showed myometrial invasion of more than 50% (p = 0.028) and positive lymphovascular invasion (p = 0.027). Similarly, more patients with co-expression of mesothelin and CA125 had myometrial invasion of more than 50% (p = 0.016) and positive lymphovascular invasion (p = 0.02). Patients with mesothelin expression and co-expression of mesothelin and CA125 demonstrated worse progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, mesothelin expression and co-expression were poor prognostic factors for PFS (mesothelin expression: hazard ratio [HR] = 2.14, p < 0.01; co-expression: HR = 2.19, p < 0.01) and OS (mesothelin expression: HR = 2.18, p < 0.01; co-expression: HR = 2.22, p < 0.01). Conclusions Mesothelin expression and co-expression might be associated with tumor aggressiveness and poor prognosis in patients with endometrial carcinoma. Persons with mesothelin-expressing endometrial cancers present a particularly high medical unmet need.

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

Cited by 31 publications

References 32 publications

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis

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