Cancer Res Treat.  2013 Jun;45(2):118-125.

Expression of Transforming Growth Factor beta1 and E-Cadherin Proteins in Pulmonary Adenocarcinoma: Its Significance in Tumor Progression

Affiliations
  • 1Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea.
  • 2Department of Radiology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
  • 3Department of Pathology, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea. jinyyoo@catholic.ac.kr

Abstract

PURPOSE
This study was conducted in order to investigate the significance of transforming growth factor beta1 (TGFbeta1) and E-cadherin proteins in tumor progression of lung adenocarcinoma and to evaluate their differential expression in association with morphologic characteristics.
MATERIALS AND METHODS
A total of 65 pulmonary adenocarcinomas were reclassified according to the new classification system proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar carcinoma [BAC]), 9 minimally invasive adenocarcinomas (MIA, formerly BAC with < or = 5 mm invasion), 17 lepidic predominant adenocarcinomas (LPA, formerly mixed adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19 invasive adenocarcinomas with no BAC features were analyzed by immunohistochemistry for expression of TGFbeta1 and E-cadherin proteins.
RESULTS
TGFbeta1 expression was detected in 46% (21/46) of noninvasive elements and 87% (39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent in invasive components than in noninvasive components (38% vs. 65%, p=0.009). Negative correlation was identified between TGFbeta1 expression and E-cadherin expression in noninvasive elements (p=0.022). More importantly, significantly higher frequency of TGFbeta1 expression was observed in noninvasive components of LPA (14/17, 82%), compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%) (p=0.008).
CONCLUSION
Our data indicate involvement of both TGFbeta1 and E-cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is noteworthy that TGFbeta1 up-regulation precedes alveolar destruction by invasion of tumor cells. TGFbeta1 may thus have the potential to improve lung adenocarcinoma diagnostics and therapeutics.

Keyword

Lung; Adenocarcinoma; Transforming growth factor beta1; Cadherins

MeSH Terms

Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Cadherins
Immunohistochemistry
Lung
Lung Neoplasms
Proteins
Transforming Growth Factor beta1
Transforming Growth Factors
Up-Regulation
Adenocarcinoma
Cadherins
Lung Neoplasms
Proteins
Transforming Growth Factor beta1
Transforming Growth Factors

Figure

  • Fig. 1 Representative immunostaining results for transforming growth factor β1 (TGFβ1) (A-D) and E-cadherin (E-H). Noninvasive component that showed negative (A) and positive (B) staining for TGFβ1. Invasive component that was negative (C) and up-regulated (D) for TGFβ1. Noninvasive element that showed lack of E-cadherin expression (E) and membranous staining (F). Invasive element that was negative (G) and positive (H) for E-cadherin expression (A-H, ABC method, ×100).


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