The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

Abstract

As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis y ), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

The potential role of podoplanin in tumour invasion

“…Podoplanin expression was also observed on squamous cell carcinomas but not adenocarcinomas of the lung (Ordonez, 2006a).…”

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

“…MOC-31, Ber-EP4, CEA, BG8 (Figure 17), and p63 are regarded as the best positive carcinoma markers for differentiating between epithelioid mesotheliomas and squamous cell carcinomas because they are commonly expressed in the latter and are usually absent in the former. 65 p63 has an advantage over the other 4 markers in that, in addition to being strongly and invariably expressed in squamous cell carcinomas, while it is absent in mesotheliomas, it may also assist in distinguishing squamous cell carcinomas from pulmonary adenocarcinomas. Because WT-1 is expressed in most epithelioid mesotheliomas, but absent in squamous cell carcinomas, it is the best positive mesothelioma marker for discriminating between these malignancies.…”

“…98,99 Occasionally, electron microscopy is useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either MM or serous carcinoma is needed. 65 Formalin-fixed material retrieved from a paraffin block may be satisfactory, since microvilli and tonofilament bundles tend to be preserved.…”

Clinical utility of diagnostic markers for malignant pleural mesothelioma

“…Thus mesothelin as a tissue marker is unable to differentiate between MPM and benign mesothelial proliferations or pleural metastases of lung cancers. Moreover 20 to 30% of epithelioid MPM are not expressing mesothelin [52] as well as all sarcomatoid MPM's [51]. Therefore its usefulness is restricted to rare situations when a panel of other markers do not give a concluding result or in some very peculiar (or "niche") applications [53][54][55].…”

“…Histological diagnosis of MPM is sometimes very difficult and immunohistochemistry using multiple (at least two positive and two negative) markers is necessary in order to provide a reliable diagnosis [50]. Despite the fact that mesothelin is intensely expressed by epithelioid mesotheliomas, its usefulness as a tumour tissue marker are very limited in practice since it is also expressed by normal mesothelial cells and by 30 to 40% of non small cell lung carcinomas [51]. Thus mesothelin as a tissue marker is unable to differentiate between MPM and benign mesothelial proliferations or pleural metastases of lung cancers.…”