Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma

Our plain-English summary of Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma, by J.A. Bishop, R. Sharma, P.B. Illei (Human Pathology, 2010).

The study

• Authors: J.A. Bishop, R. Sharma, P.B. Illei
• Journal: Human Pathology
• Published: 2010;41(1):20-5
• Cited by: 250 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Recent advances in the treatment of pulmonary adenocarcinoma have increased the need for accurate typing of non-small cell carcinomas. Immunohistochemistry for thyroid transcription factor-1 is widely used in the diagnosis of pulmonary adenocarcinomas because it marks approximately 75% of lung adenocarcinomas and is negative in most squamous cell carcinomas and adenocarcinomas of other organs. Napsin A is an aspartic proteinase involved in the maturation of surfactant protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar macrophages and is a putative marker for pulmonary adenocarcinomas. We performed immunohistochemistry for napsin A and thyroid transcription factor-1 using tissue microarrays of 95 adenocarcinomas, 48 squamous cell carcinomas, 6 neuroendocrine tumors of the lung, as well as 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas, 38 malignant mesotheliomas, 118 renal cell carcinomas, and 81 thyroid tumors. The tissue microarrays also included 15 different benign tissues. Pulmonary adenocarcinomas were napsin A positive in 79 (83%) of 95 cases compared with 69 (73%) of 95 cases that were thyroid transcription factor-1 positive. There were 13 napsin A-positive/thyroid transcription factor-1-negative and 2 thyroid transcription factor-1-positive/napsin A-negative tumors, increasing the number of cases that were positive with at least one of the markers to 81 (85%) of 95. The limited number of neuroendocrine tumors tested was napsin A negative. All squamous cell carcinomas, adenocarcinomas of the colon, pancreas and breast, and mesotheliomas were negative for both markers. Of the renal tumors, napsin A was positive in most of papillary renal cell carcinomas (79%), about one third (34%) of clear cell renal cell carcinomas, and in a single case of chromophobe renal cell carcinoma (3%). In the thyroid, only 2 cases of papillary thyroid carcinoma (5%), both with tall cell morphology, were positive for napsin A, whereas all other papillary and follicular carcinomas were negative. As expected, all renal tumors were thyroid transcription factor-1 negative, and all thyroid tumors, except for one papillary carcinoma, were thyroid transcription factor-1 positive. Napsin A is a sensitive marker for pulmonary adenocarcinoma and is also expressed in a subset of renal cell carcinomas, particularly of the papillary type, as well as in rare cases of papillary thyroid carcinomas. The combined use of napsin A and thyroid transcription factor-1 results in improved sensitivity and specificity for identifying pulmonary adenocarcinoma in primary lung tumors and in a metastatic setting.

In plain English

This laboratory pathology study, from The Johns Hopkins Medical Institutions, did not examine asbestos exposure. It tested whether two tissue stains, napsin A and thyroid transcription factor-1 (TTF-1), help identify adenocarcinoma that began in the lung. The authors stained small tissue samples from archived specimens. These included 95 lung adenocarcinomas, other lung cancers, cancers of the colon, pancreas, breast, kidney and thyroid, and 38 malignant mesotheliomas (33 pleural and 5 peritoneal). Napsin A was positive in 79 of 95 lung adenocarcinomas (83%) and TTF-1 in 69 of 95 (73%). Together, 81 (85%) were positive for at least one stain. All 38 mesotheliomas were negative for both stains, as were the breast, colon and pancreas adenocarcinomas. Napsin A was positive in 79% of papillary and 34% of clear cell kidney cancers, and in 2 papillary thyroid carcinomas. The authors concluded that napsin A is best used together with TTF-1. They noted that too few neuroendocrine tumors were tested to draw conclusions, and that napsin A also stains some tumors that did not start in the lung.

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: Laboratory immunohistochemistry study of archived tumor tissue arranged in tissue microarrays (not an epidemiological or asbestos exposure study)
• Who was studied: Archived surgical specimens from The Johns Hopkins Hospital, Baltimore: 173 primary lung tumors (including 95 adenocarcinomas, 48 squamous cell carcinomas and 6 neuroendocrine tumors), 38 malignant mesotheliomas (29 epithelioid, 6 biphasic, 3 sarcomatoid; 33 pleural, 5 peritoneal), 118 renal cell carcinomas, 81 thyroid tumors, 5 colon, 31 pancreas and 17 breast adenocarcinomas, and 15 benign tissues. No dates are given.
• Exposure: No asbestos or other exposure was studied. Tissues were stained with antibodies to napsin A and TTF-1 and scored for intensity and extent.
• Main results:
  • Lung adenocarcinomas: napsin A positive in 79 of 95 (83%); TTF-1 positive in 69 of 95 (73%)
  • Lung adenocarcinomas: 81 of 95 (85%) were positive for at least one of the two stains
  • Lung adenocarcinomas: both stains were positive less often in higher-grade tumors (poorly differentiated: napsin A 11/16, 69%; TTF-1 7/16, 44%, per Table 2)
  • Malignant mesothelioma (all types, 0/38) and breast, colon and pancreas adenocarcinomas were negative for both stains
  • All lung squamous cell carcinomas were negative for both stains
  • Kidney cancers: napsin A positive in 79% of papillary (34/43) and 34% of clear cell (14/41) renal cell carcinomas, and in 1 chromophobe (1/34). TTF-1 was negative in all renal tumors.
  • Thyroid: napsin A positive in 2 papillary thyroid carcinomas, both with tall cell morphology
  • Lung neuroendocrine tumors: napsin A negative in all 6 tested
• The authors' conclusion: The authors concluded that napsin A is best used together with TTF-1 to diagnose lung adenocarcinoma
• Limitations the authors state:
  • Too few neuroendocrine tumors were included to draw conclusions about the lack of napsin A staining in them
  • It is unclear whether the lower positivity in higher-grade tumors reflects true antigen expression, sampling, tissue fixation, or a combination
  • Napsin A also stains some tumors that did not start in the lung (kidney and thyroid)

Topics

Medical terms in this study, explained in our Lexicon: Thyroid Transcription Factor-1 (TTF-1), Carcinoma, Malignant Mesothelioma, Adenocarcinoma, Immunohistochemistry, Lung Adenocarcinoma, Squamous Cell Carcinoma, Alveolar Macrophage.

Related studies

• Expression of thyroid transcription factor-1 in malignant pleural effusions — A. Khoor, A.L. Byrd-Gloster, et al. (2011)
• Gene expression of surfactant protein-A and thyroid transcription factor-1 in lungs of rats exposed to silicon-carbide whisker in vivo — Y. Morimoto, L. Ding, et al. (2003)
• An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma — S. Klebe, A. Swalling, et al. (2016)
• Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma — N.G. Ordóñez (2013)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas — D.G. Davis, M.T. Siddiqui, et al. (2016)

Browse more research in Human Pathology, or return to medical research.