Bejarano PA, Baughman RP, Biddinger PW, Miller MA, Fenoglio-Preiser C, al-Kafaji B, Di Lauro R & Whitsett JA

 Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. 

Mod Pathol, 9, 445-452,1996
Abstract: Antibodies to the pulmonary epithelial cell-specific proteins surfactant proteins A and B (SP-A and SP-B) and to thyroid transcription factor-1 (TTF-1), a homeodomain nuclear transcription protein, were used as immunohistochemical markers to asses their ability to distinguish primary pulmonary non-small cell carcinomas (n = 57) from carcinomas of the breast (n = 51). SP-A, SP-B, and TTF-1 were detected in 49%, 53%, and 63% of non-small cell carcinomas, respectively. These three antibodies stained pulmonary adenocarcinomas in 54%, 63% and 76% of specimens, respectively. Squamous cell carcinomas rarely stained using these markers. Antibodies to SP-B and TTF-1 never stained any of the 51 breast carcinomas, whereas four of these tumors stained for SP-A. To better define the potential diagnostic value of these antibodies, 13 breast carcinomas metastatic to the lung were studied. Of the three antibodies tested, only TTF-1 seemed useful, because none of the 13 metastatic tumors showed immunoreactivity to this antibody, whereas six specimens (46%) showed reactivity for both SP-A and SP-B. To emphasize further the potential usefulness of antibodies to TTF-1, sections of adenocarcinomas of the colon (n = 18) and prostate (n = 9), renal cell carcinomas (n = 8), and epithelioid mesotheliomas (n = 4) were evaluated; none was positive. Only one of 66 gastric and one of eight endometrial adenocarcinomas showed focal positivity. These results demonstrate the usefulness of immunodetection of a pulmonary cell selective transcription protein (TTF-1) in the diagnosis of pulmonary adenocarcinoma, readily distinguishing breast carcinomas from primary pulmonary adenocarcinomas. In contrast, staining for SP-A and SP-B is of limited value, because there is an unacceptably high rate of cross-reactivity between breast carcinomas metastatic to the lung and primary pulmonary carcinomas. The latter finding illustrates and supports the fact that tumor marker phenotypes might differ in primary and secondary tissue sites

Chhieng DC, Cangiarella JF, Zakowski MF, Goswami S, Cohen JM & Yee HT 

Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens. 

Cancer 93, 330-336,2001
Abstract: BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining

 

 

Harlamert HA, Mira J, Bejarano PA, Baughman RP, Miller MA, Whitsett JA & Yassin R 

Thyroid transcription factor-1 and cytokeratins 7 and 20 in pulmonary and breast carcinoma. 

Acta Cytol, 42, 1382-1388,1998
Abstract: OBJECTIVE: To evaluate the immunohistochemical expression of a lung epithelial gene transcription factor, thyroid transcription factor-1 (TTF-1), in lung and breast carcinoma in pulmonary cytologic preparations and to correlate the results with the expression of cytokeratin 7 (CK7) and 20 (CK20). STUDY DESIGN: Cell blocks of cytologic specimens were immunostained with antibodies to TTF-1, CK7 and CK20. Specimens included 41 primary lung carcinomas (21 adenocarcinomas, 8 squamous cell carcinomas and 12 small cell undifferentiated carcinomas) and 6 metastatic breast adenocarcinomas. RESULTS: The lung adenocarcinomas showed nuclear reactivity for TTF-1 in 76% (16/21) of the cases and a staining combination of CK7+/CK20- in 95% (20/21) of the cases. Only one case was CK7+/CK20+. All the breast carcinomas were nonreactive to TTF-1, and all were CK7+/CK20-. The squamous cell carcinomas and small cell undifferentiated carcinomas showed TTF-1 positivity in 38% (3/8) and 83% (10/12), respectively

 

 

Kaufmann O & Dietel M 

Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. 

Histopathology 36, 415-420,2000.
Abstract: AIMS: The thyroid transcription factor-1 (TTF-1) is a highly specific immunohistochemical marker for the identification of pulmonary adenocarcinomas and non-neuroendocrine large cell carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site. In this study we tested if anti-TTF-1 can also be used to verify a pulmonary origin of neuroendocrine carcinomas, placing emphasis on the discrimination of pulmonary small cell carcinomas (SCCs) from extrapulmonary SCCs and the distinction of SCCs from Merkel cell carcinomas of the skin. METHODS AND RESULTS: We studied 37 pulmonary SCCs, 15 SCCs of extrapulmonary origin, 4 pulmonary large cell neuroendocrine carcinomas (LCNECs), four extrapulmonary LCNECs, six medullary thyroid carcinomas, 16 Merkel cell carcinomas, and a total of 32 carcinoids/low-grade neuroendocrine carcinomas of pulmonary (12 cases) and extrapulmonary (20 cases) origin. Using the commercially available monoclonal antibody 8G7G3/1, TTF-1 was immunohistochemically detectable in 81% of pulmonary SCCs but also in 80% of extrapulmonary SCCs. Furthermore, anti-TTF-1 showed a positive staining in 50% of all pulmonary carcinoids, in one gastric carcinoid, in 2/4 of pulmonary, and 1/4 of extrapulmonary LCNECs. All medullary thyroid carcinomas were also TTF-1-positive. Merkel cell carcinomas were consistently TTF-1-negative. CONCLUSIONS: Our results suggest that in contrast to non-neuroendocrine carcinomas, anti-TTF-1 cannot be used to prove or to exclude a pulmonary origin of SCCs or LCNECs of unknown or uncertain primary site. Therefore, before using anti-TTF-1 as a marker for pulmonary carcinomas one should be sure to have excluded SCC and LCNEC. On the other hand, anti-TTF-1 might be used to specifically discriminate SCCs of various origin from Merkel cell carcinomas

 

 

Reis-Filho JS, Carrilho C, Valenti C, Leitao D, Ribeiro CA, Ribeiro SG & Schmitt FC 

Is TTF1 a good immunohistochemical marker to distinguish primary from metastatic lung adenocarcinomas? 

Pathol Res Pract, 196, 835-840,2000
Abstract: To evaluate the immunohistochemical expression of thyroid transcription factor 1 (TTF1) in primary and metastatic pulmonary adenocarcinomas, and test the diagnostic accuracy of this antibody, two surgical pathologists independently evaluated 34 cases of adenocarcinomas in the lung without clinical data and tried to distinguish between primary and metastatic cases using histological criteria exclusively. Thirteen cases were primary in the lung and 21 were metastases of extrapulmonary adenocarcinomas: 6 from the endometrium, 4 from the ovary, 3 from the colon, 2 from the kidney, 2 from the breast, 2 from the liver and 1 from the prostate. Afterward, the immunoreactivity of TTF1 in these neoplasms was evaluated and correlated with morphological and clinical data. The two pathologists were able to diagnose only 5 out of 13 cases of primary lung adenocarcinomas (sensitivity of 38.46%) and also misdiagnosed two primary malignancies as metastases. After correlation with TTF1 data, the sensitivity increased to 61.53%. The specificity of TTF1 was 100%. In conclusion, TTF1 is a highly specific marker for primary lung adenocarcinomas, and should be included in a panel of antibodies for the differential diagnosis between primary and metastatic adenocarcinomas of the lung