Calretinin-expressing lung adenocarcinoma: Distinct characteristics of advanced stages, smoker-type features, and rare expression of other mesothelial markers are useful to differentiate epithelioid mesothelioma

Abstract

Calretinin, a mesothelioma marker, is sometimes expressed in lung cancer, which may complicate the differential diagnosis of mesothelioma. Here, the clinicopathological and immunohistochemical characteristics of calretinin-positive lung cancer were examined to reduce confusion with malignant mesothelioma. Calretinin expression in 307 consecutive cases of lung cancer was evaluated immunohistochemically. Survival was analyzed using the Kaplan–Meier method and log-rank test. Calretinin expression was identified in 67 (22%) tumors, including those with partial and weak expression [15% (37/250) of adenocarcinomas, 54% (25/46) of squamous cell carcinomas, 75% (3/4) of adenosquamous carcinomas, and 29% (2/7) of sarcomatoid carcinomas]. In calretinin-positive adenocarcinoma (n = 37), expression percentages of Wilms tumor-1, podoplanin, thyroid transcription factor-1, and claudin-4 were 6, 3, 52, 82%, respectively, whereas in calretinin-positive squamous cell carcinoma (n = 25) the percentages were 8, 12, 12, 68%, respectively, indicating that other mesothelial markers were only rarely expressed and that claudin-4 expression was common. Although not an independent marker, calretinin expression was associated with a poor prognosis for stage I tumors of adenocarcinoma (p < 0.001) and of all histological subtypes (p < 0.001). In conclusion, calretinin-positive lung tumors share characteristics with those of smokers and advanced stages and can be differentiated from mesothelioma with the use of other mesothelial and epithelial markers.