Thyroid Transcription Factor-1 (TTF-1) Expression in Human Lung Carcinomas: Its Prognostic Implication and Relationship with Expressions of p53 and Ki-67 Proteins

Myong, Na Hye

doi:10.3346/jkms.2003.18.4.494

Cited by 66 publications

(66 citation statements)

References 28 publications

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“…33,34 The prognostic value of TTF-1 was evaluated in non-small-cell carcinomas, and contradictory results were reported. 35,36 We found that TTF-1 was detectable in 33% of classic large cell carcinoma cases, 24% of large cell neuroendocrine carcinoma, and 57% in small cell carcinoma. TTF-1 had a poor prognostic implication in small cell carcinoma in our study.…”

Section: Discussionmentioning

confidence: 76%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

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Section: Discussionmentioning

confidence: 76%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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“…TTF-1 is generally expressed diffusely in thyroid tumors but TTF-1 immunoreactivity varies according to tumor type in lung tumors (6). The TTF-1 immunoreactivity rate in primary lung ACs has been reported to be 60% to 100% (6,(38)(39)(40)(41). Studies reporting a lower staining percentage have emphasized the reason as TTF-1 immunoreactivity being lower in mucinous ACs compared to nonmucinous cases (38)(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 92%

“…The TTF-1 immunoreactivity rate in primary lung ACs has been reported to be 60% to 100% (6,(38)(39)(40)(41). Studies reporting a lower staining percentage have emphasized the reason as TTF-1 immunoreactivity being lower in mucinous ACs compared to nonmucinous cases (38)(39)(40)(41)(42). TTF-1 is widely utilized in the identification of ACs of lung origin as TTF-1 has been determined to be negative in extra-pulmonary ACs other than some rare ovarian carcinomas (6,43).…”

Section: Discussionmentioning

confidence: 99%

Expression of p63, ttf–1 and maspin in non-small cell lung carcinoma and their effect on the prognosis and differential diagnosis

Yaman¹,

Nart²,

Ekren³

et al. 2015

TJPATH

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Objective: Lung cancer is still the leading cause of cancer mortality. Antiapoptotic genes and protease inhibitors play an important role in the development of lung cancer.Material and Method: p63, TTF-1 and maspin expression and their role in the differential diagnosis, overall survival, progression-free survival and other clinicopathological characteristics of the patients were investigated in 80 surgically-resected non-small cell lung carcinomas. Results:The maximal tumor diameter range was 1.5-11 cm (mean: 4.06±1.8 cm). Forty-five (56.3%) tumors were adenocarcinoma, 23 (28.8%) squamous cell carcinoma, four (5%) large cell carcinoma, six (7.5%) large cell neuroendocrine carcinoma, one (1.2%) sarcomatoid carcinoma while one was (1.2%) both adenocarcinoma and squamous cell carcinoma. The patients with advanced TNm stage and a tumor diameter more than 3 cm had markedly poor survival. Immunohistochemically, p63 staining was present in 87.5% of squamous cell carcinomas, 4.3% of adenocarcinomas, 25% of large cell carcinomas, and 16.7% of large cell neuroendocrine carcinomas. Similarly, maspin was positive in 66.7% of squamous cell carcinomas and 17.4% of adenocarcinomas. The TTF-1 staining rate was higher in adenocarcinomas (84.8%). There was no immunoreactivity in squamous cell carcinomas (p<0.001). We found that p63 and TTF-1 had no significant effect on survival in either tumor group (p>0.05) while maspin has a negative prognostic effect in adenocarcinoma (p=0.048). Conclusion:This study suggests that p63 and TTF-1 are reliable markers in non-small cell lung carcinoma and can be used in differential diagnosis. maspin has been identified as a prognostic marker in adenocarcinoma. However, more studies are required to elucidate the significance of maspin.Key Words: Non-small-cell lung carcinoma, p63, TTF-1, maspin, Prognosis ÖZ Amaç: Akciğer kanseri, kanser ölümlerinin önde gelen nedenlerindendir. Antiapopitotik genler ve proteaz inhibitörleri akciğer kanseri gelişiminde önemli role sahiptir. Gereç ve Yöntem:Seksen opere küçük hücreli dışı akciğer karsinom olgusunda p63, TTF-1 ve maspin ekspresyonunun ayırıcı tanıya olan katkıları, sağkalım ve hastalıksız sağkalım üzerine etkileri ve diğer klinikopatolojik özellikler değerlendirildi. Bulgular:Ameliyat materyallerinde izlenen tümörlerin çapları 1,5-11 cm arasında (ort. 4,06±1,8) olup, 45 (%56,3) adenokarsinom, 23 (%28,8) skuamöz hücreli karsinom, dört (%5) büyük hücreli karsinom, altı (%7,5) büyük hücreli nöroendokrin karsinom, bir (%1,2) sarkomatoid karsinom ve bir (%1,2) adenokarsinom ve skuamöz hücreli karsinom birlikteliğinden oluşmakta idi. İleri TNm evreli ve üç cm' den daha büyük tümör çapı olan olgular daha kötü prognozlu idi. İmmünohistokimyasal incelemede skuamöz hücreli karsinomların %87,5'i, adenokarsinomların %4,3'ü, büyük hücreli karsinomların %25'i ve büyük hücreli nöroendokrin karsinomların %16,7'si p63 ile pozitif boyandı. Benzer olarak maspin de skuamöz hücreli karsinomlarda %66,7 ve adenokarsinomlarda %27,4 oranında pozitifti. TTF-1 ekspre...

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“…A positive TTF1 staining has been inversely related to the proliferative activity evaluated through Ki-67 expression, usually considered as a marker of poor prognosis in NSCLC (Pelosi et al, 2001;Myong, 2003). On the other hand, a correlation between positive TTF1 staining and various molecular markers expression such as p53 or HER2/neu involved in lung carcinogenesis has been suggested (Haque et al, 2002;Yatabe et al, 2002;Myong, 2003). Thus, further biological investigations are needed.…”

Section: Discussionmentioning

confidence: 99%

“…A study on 222 stage I NSCLC patients demonstrated no survival difference associated with TTF1 immunoreactivity (Pelosi et al, 2001), while another study correlated a positive TTF1 staining of resected NSCLC with a poor survival (Puglisi et al, 1999). On the other hand, four studies on early stages of NSCLC associated a positive TTF1 staining with a longer survival (Haque et al, 2002;Myong, 2003;Tan et al, 2003;Saad et al, 2004). However, all these studies were interested in surgical NSCLC patients and all but one (Saad et al, 2004) included both ADC and non-ADC histological types of NSCLC.…”

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confidence: 99%

Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

et al. 2005

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This study investigated the relation between positive thyroid transcription factor 1 (TTF1) staining and survival of patients affected by primary adenocarcinoma (ADC) of the lung. Pathological tissue from consecutive ADC patients was collected from 2002 to 2004. The anti-TTF1 antibody (8G7G3/1, dilution of 1/200) was used. Thyroid transcription factor 1 staining was assessed for each tumour as positive or negative. Probability of survival was estimated by Kaplan -Meier and difference tested by log-rank test. A Cox's regression multivariate analysis was carried out. In all, 106 patients were studied (66% male, 69% PS0 -1, 83% with stage III or IV). Tumours expressed positive TTF1 staining in 66% of cases. Multivariate analysis demonstrated an independent lower risk of death for patients whose tumour expresses positive TTF1 staining (HR ¼ 0.51, 95% CI 0.30 -0.85; P ¼ 0.01) and higher grade of differentiation (HR ¼ 0.40, 95% CI 0.24 -0.68; P ¼ 0.001). In conclusion, positive TTF1 staining strongly and independently correlates with survival of patients with primary ADC of the lung.

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Thyroid Transcription Factor-1 (TTF-1) Expression in Human Lung Carcinomas: Its Prognostic Implication and Relationship with Expressions of p53 and Ki-67 Proteins

Cited by 66 publications

References 28 publications

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Expression of p63, ttf–1 and maspin in non-small cell lung carcinoma and their effect on the prognosis and differential diagnosis

Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

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