Selective Immunohistochemical Markers to Distinguish Between Metastatic High-Grade Urothelial Carcinoma and Primary Poorly Differentiated Invasive Squamous Cell Carcinoma of the Lung

Abstract

N Context.-Distinction between primary lung carcinomas and metastases from other sites, especially the urinary tract, is a common diagnostic dilemma. As urothelial carcinomas can demonstrate a broad range of morphology and frequently demonstrate squamous differentiation, discerning metastatic urothelial carcinoma to the lung from primary pulmonary squamous cell carcinoma can be challenging.Objective.-To investigate immunostains that may aid in the distinction of urothelial carcinoma metastatic to the lung.Design.-Staining patterns of 14 markers in primary urothelial carcinoma of the bladder and primary squamous cell carcinoma of the lung were examined to establish a diagnostic panel. These antibodies were subsequently tested on tumors taken from 30 patients with a paired urinary tract and metastatic lung lesion.Results.-The best markers to distinguish poorly differentiated metastatic urothelial carcinoma from primary pulmonary squamous cell carcinoma were CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III, with the utility of the latter dependent upon the quantity of tissue available for analysis. The observed percentage positive staining in nonmetastatic urothelial carcinoma versus primary pulmonary squamous cell carcinoma with these antibodies was as follows: CK7 (100% versus 33%), CK20 (54% versus 7%), GATA-3 (78% versus 23%), CK14 (32% versus 77%), desmoglein-3 (11% versus 87%), and uroplakin III (14% versus 0%). Similar expression patterns were observed among the paired cases.Conclusion.-When interpreted in correlation with clinical history and histomorphology, a panel of immunostains including CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III may be a useful adjunct in the distinction of metastatic urothelial carcinoma to the lung.

GATA3 Immunohistochemical Expression in Salivary Gland Neoplasms

“…Initial studies demonstrated that GATA3 immunostaining was seen in a limited number of tumor types: mammary carcinoma, urothelial carcinoma, and a minority of endometrial carcinomas [8,9,16]. Subsequent studies have expanded the list of GATA3-positive tumors to include occasional squamous cell carcinomas of the anus, cervix, and lung [11,12]. By performing immunohistochemistry on a large and diverse collection of salivary gland tumors, we found that approximately half were immunoreactive for GATA3.…”

“…Accordingly, GATA3 immunohistochemical staining is being used as a practical tool for diagnosing breast and urothelial carcinoma, particularly when these tumors present as distant metastases or are so poorly differentiated that they cannot be distinguished from other tumor types [10][11][12]. Various studies across a broad spectrum of diverse tumor types have confirmed the restricted expression of GATA3 staining to breast and urothelial origin, but these studies have curiously not included salivary gland neoplasms [1][2][3][4][5][6][7][8][9][10][11][12]. Mammary glands and salivary glands are both ectodermally-derived exocrine secretory structures that share many embryologic, histologic, and immunohistochemical features.…”

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

“…72 Chang et al 75 reported the same finding. However, the study by Gruver et al 76 reported 23% of pulmonary SCCs can be positive for GATA3. More recent studies demonstrated that GATA3 expression was seen in (1) salivary gland tumors (100% of salivary ductal carcinomas and mammary analogue secretory carcinomas), 74 (2) 80% of metastatic paragangliomas, 73 and (3) 7% of anal SCCs and 19% of uterine cervical SCCs, which tended to be focally positive.…”

Differences in Expression of Uroplakin III, Cytokeratin 7, and Cyclooxygenase-2 in Canine Proliferative Urothelial Lesions of the Urinary Bladder

“…49,52 Uroplakin III (UPIII) and CK7 are used in dogs and humans as diagnostic markers of urothelial differentiation in primary tumors and metastases. 8,13,31,35,39,47 In humans, loss of UPIII has been associated with several prognostic features. 13,25 The inducible enzyme cyclooxygenase-2 (COX-2) and the resulting production of prostaglandin E 2 have been ascribed significant roles in carcinogenesis, including immunosuppression, inhibition of apoptosis, increased metastatic potential of neoplastic epithelial cells, promotion of drug resistance, and stimulation of angiogenesis.…”

“…8,13,31,35,39,47 In humans, loss of UPIII has been associated with several prognostic features. 13,25 The inducible enzyme cyclooxygenase-2 (COX-2) and the resulting production of prostaglandin E 2 have been ascribed significant roles in carcinogenesis, including immunosuppression, inhibition of apoptosis, increased metastatic potential of neoplastic epithelial cells, promotion of drug resistance, and stimulation of angiogenesis. 9,11,23,[54][55][56] Numerous studies have shown significant correlations between COX-2 expression and tumor grade, infiltration, metastasis, and survival.…”