Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors

doi:10.1053/hupa.2001.28245

Human Pathology

Volume 32, Issue 10, October 2001, Pages 1087-1093

https://doi.org/10.1053/hupa.2001.28245 Get rights and content

Abstract

Expression of cytokeratin (CK) 7 and 20 is commonly used to help distinguish adenocarcinomas from different sites. Thyroid transcription factor 1 (TTF-1) is a 38-kd protein, located primarily in the nucleus of type 2 pneumocytes and clara cells. TTF-1 has been shown to be present in a variety of lung and thyroid tumors and in pulmonary small-cell carcinomas. Carcinoid tumors from the lung and the gastrointestinal (GI) tract are histologically similar and thus are difficult to differentiate from each other based on histologic criteria. Pancreatic endocrine tumors (PET) have a similar histologic appearance to these other tumors. The purpose of this study was to determine the efficacy of differentiating these 3 groups of tumors by their expression of CK7, CK20, and TTF-1. Routinely processed paraffin-embedded tissue sections from 62 carcinoid tumors (lung, 16; gastrointestinal [GI] tract, 46) and 12 PETs were immunohistochemically stained for CK7, CK20, and TTF-1. The degree of expression in each tumor was graded as 1+ (1% to 10% of cells positive), 2+ (11% to 25%), 3+ (26% to 50%), and 4+ (>50%). The data were compared between tumor types and between carcinoid tumors from the various locations in the GI tract (stomach, 8; small intestine, 19; large intestine, 17; appendix, 2). CK7 was expressed in 10 (63%) of 16 pulmonary carcinoid tumors and only 5 (11%) of 46 GI carcinoid tumors (P <.001). Pancreatic endocrine tumors showed CK7 positivity in 6 (50%) of 12 cases, which was similar to the findings in lung carcinoids and significantly higher than in GI carcinoids (P <.01). CK20 was expressed in 0 (0%) of 16 pulmonary carcinoid tumors, in contrast to 24% and 33% of GI carcinoid tumors (P <.05) and PETs (P <.05), respectively. TTF-1 expression was highly specific for pulmonary carcinoid tumors. This peptide was present in 11 (69%) of 16 pulmonary carcinoid tumors and in only 1 (2%) of 46 and 0 (0%) of 12 GI carcinoid tumors (P <.001) and PETs (P <.001), respectively. A CK7⁺/CK20⁻/TTF-1⁺ immunopanel result was moderately sensitive (sensitivity, 50%), and highly specific (specificity, 100%), for a diagnosis of pulmonary carcinoid tumor. CK7, CK20, and TTF-1 did not differ significantly between carcinoid tumors located in different sites of the GI tract. However, a trend was observed toward a lower prevalence of CK20 positivity in gastric tumors (P =.06) than in GI carcinoid tumors from the small intestine, colon, or appendix. Expression of CK7 and CK20, and particularly TTF-1, may be useful in distinguishing pulmonary from GI carcinoid tumors and PETs, especially when evaluated as a panel of markers. TTF-1 is highly specific for pulmonary carcinoid tumors. HUM PATHOL 32:1087-1093. Copyright © 2001 by W.B. Saunders Company

Section snippets

Study groups

Sixty-two carcinoid tumors (lung, 16; GI tract, 46) and 12 PETs were collected from the surgical pathology files of the Brigham and Women's Hospital (Boston, MA) and University of Massachusetts Memorial Healthcare Center (Worcester, MA). The diagnosis of carcinoid tumor or PET was established by histologic analysis in conjunction with the finding of immunoreactivity for chromogranin and/or synaptophysin according to the criteria of Capella et al.¹⁸ In all lung cases, the carcinoid tumors were

Pulmonary carcinoid tumors

Thirty-eight percent of patients were male (Table 1).Their ages ranged from 49 to 85 years, with a mean age of 67 years. The tumors averaged 1.6 cm in size (range, 0.4 to 6 cm). All but 1 of the tumors were well differentiated. The other was an atypical carcinoid tumor. One case had regional lymph node metastasis, and another had liver metastasis. Most (88%) of the cases were stage I.

CK7 was expressed in 10 (63%) of 16 pulmonary carcinoid tumors (Table 2).Immunostaining was restricted to the

Discussion

Over the last decade, the expression of CKs in tumor cells has been used to help determine the primary location of a metastatic carcinoma and confirm the epithelial nature of an unknown tumor.1, 4 For instance, the immunostaining profile of CK7 and CK20 is widely used to help distinguish pulmonary from colonic adenocarcinomas.¹⁵ Strong expression of CK7 favors a lung primary tumor, expression of CK20 favors a colon primary. In addition, TTF-1 has recently been proposed to help distinguish a

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^☆: Address correspondence and reprint requests to Robert D. Odze, MD, Department of Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.

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Original ContributionsCytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors☆

Abstract

Section snippets

Study groups

Pulmonary carcinoid tumors

Discussion

Cell

Mod Pathol

Int J Biochem Cell Biol

Hum Pathol

Mod Pathol

Identification of protein IT of the intestinal cytokeratin as a novel type I cytokeratin with unusual properties and expression patterns

J Cell Biol

An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumors. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas

Histopathology

Intermediate- and low-molecular-weight keratin detection with the monoclonal antibody MNF116. An immunohistochemical study on 232 paraffin-embedded cutaneous lesions

J Cutan Pathol

Keratin 20: Immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas

Mod Pathol

The transcription factor TTF-11 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the fetal brain

Development

The lung-specific protein B promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating commong factors for organ specific gene expression along the foregut axis

Mol Cell Biol

Lung cell specific expression of the murine surfactant protein A (SP-A) gene is mediated by interaction between the SP-A promoter and thyroid transcription factor-1

J Biol Chem

Regulation of clara cell secretory protein gene transcription by thyroid transcription factor-1

Biochim Biophys Acta

Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies

Am J Pathol

Original Contributions
Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors☆