Expression of Calretinin, Marker of Mesothelial Differentiation, in Pancreatic Ductal Adenocarcinoma: A Potential Diagnostic Pitfall

Our plain-English summary of Expression of Calretinin, Marker of Mesothelial Differentiation, in Pancreatic Ductal Adenocarcinoma: A Potential Diagnostic Pitfall, by G. Askan, O. Basturk (Türk Patoloji Dergisi, 2021).

The study

• Authors: G. Askan, O. Basturk
• Journal: Türk Patoloji Dergisi
• Published: 2021;37(2):115-120
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Pancreatic ductal adenocarcinoma is one of the most common causes of "peritoneal carcinomatosis" and has an insidious growth pattern. Thus, it falls into the differential diagnosis of other peritoneal malignancies including malignant mesothelioma. Recently, we have encountered an undifferentiated pancreatic carcinoma presenting with peritoneal disease and exhibiting immunoreactivity to calretinin, mimicking mesothelioma. In this study, we explored the incidence of calretinin expression in pancreatic ductal adenocarcinoma.

Materials And Methods: Calretinin immunohistochemical staining was performed on the tissue microarrays (TMAs), which were created using three 0.6 mm diameter punches per tumor (n=113). Distribution and intensity of expression were evaluated.

Results: The TMAs contained 86 well/moderately differentiated and 27 poorly differentiated/undifferentiated carcinomas. Calretinin was positive in nine tumors (8%); six with diffuse and strong staining, three with focal and/or weak staining. The incidence of calretinin expression was 15% in poorly differentiated/undifferentiated carcinomas (vs. 6% in well/moderately differentiated carcinomas, p=0.03).

Conclusions: Pancreatic ductal adenocarcinomas, especially when poorly differentiated/undifferentiated, may be diffusely and strongly positive for calretinin creating a potential diagnostic challenge with malignant mesothelioma. Therefore, caution should be exercised when using this marker to explore a diagnosis of malignant mesothelioma. Tumors expressing calretinin without other mesothelial markers should prompt a careful evaluation of the morphologic and immunohistochemical features to exclude other malignancies. If the diagnosis of pancreatic ductal adenocarcinoma is considered, ductal differentiation can be demonstrated by using additional immunohistochemical markers such as mucin-related glycoproteins (MUC1, MUC5AC) and/or oncoproteins (CEA, B72.3, CA125).

In plain English

This laboratory pathology study, from Memorial Sloan Kettering Cancer Center, asked whether pancreatic ductal adenocarcinoma stains for calretinin. This pancreatic cancer can spread across the lining of the abdomen, and calretinin is a protein pathologists use as a marker of malignant mesothelioma. The study did not examine asbestos exposure. The authors stained tissue from 113 archived pancreatic tumors for calretinin and for two other mesothelioma markers, D2-40 and WT-1. Calretinin was found in 9 of the 113 tumors (8%), six of them with diffuse and strong staining. The article reports calretinin staining in 15% of poorly differentiated or undifferentiated tumors, compared with 6% of well or moderately differentiated tumors (p=0.03). Only one tumor stained for D2-40, and that tumor was calretinin-negative. No tumor stained for WT-1. Calretinin-positive and calretinin-negative cases did not differ significantly in age, tumor size, lymph node spread or overall survival. The authors concluded that these pancreatic cancers can be diffusely and strongly positive for calretinin, creating a diagnostic pitfall. In their view, calretinin staining without other mesothelial markers should prompt careful evaluation to exclude other cancers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective immunohistochemistry study of archived pancreatic tumors arranged on tissue microarrays
• Who was studied: 113 pancreatic ductal adenocarcinomas from the pathology files of Memorial Sloan Kettering Cancer Center, New York (86 well/moderately differentiated, 27 poorly differentiated/undifferentiated); years of the cases not stated
• Exposure: No asbestos or other environmental exposure was studied. Tumors were stained with antibodies against calretinin and two other mesothelioma markers, D2-40 and WT-1.
• Main results:
  • Calretinin was positive in 9 of 113 pancreatic ductal adenocarcinomas (8%): 6 with diffuse and strong staining, 3 with focal and/or weak staining
  • Of the 9 calretinin-positive tumors, 5 were poorly differentiated/undifferentiated and 4 were moderately differentiated. The article reports calretinin expression in 15% of poorly differentiated/undifferentiated carcinomas versus 6% of well/moderately differentiated carcinomas (p=0.03).
  • Only one of the 113 tumors expressed D2-40, and it was calretinin-negative. None of the 113 expressed WT-1.
  • Calretinin-positive (n=9) and calretinin-negative (n=104) cases were similar in mean age (66.6 vs. 67.8 years, p=0.62), median tumor size (3 cm in both, p=0.54) and lymph node metastasis (78% vs. 69%, p=0.71). The female:male ratio was 2:1 vs. 1:1 (p=0.49).
  • Overall survival did not differ significantly between calretinin-positive and calretinin-negative cases (p=0.19). Of the 9 calretinin-positive patients, 5 died of the disease and 4 were alive with no evidence of disease.
• The authors' conclusion: The authors concluded that pancreatic ductal adenocarcinomas can be diffusely and strongly positive for calretinin, creating a diagnostic pitfall, especially when poorly differentiated or undifferentiated. In their view, tumors expressing calretinin without other mesothelial markers such as D2-40 and WT-1 should prompt careful evaluation to exclude other peritoneal malignancies.

Topics

Medical terms in this study, explained in our Lexicon: Calretinin, Adenocarcinoma, Differential Diagnosis, Mesothelioma, Carcinoma, Immunohistochemistry, Glycoprotein, B72.3 (TAG-72).

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