Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 8, Issue 2, Pages 152-160Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0b013e318279d503
Keywords
Non-small cell lung cancer; LYPD3; Histologic subtypes of adenocarcinomas; Survival; Biomarker
Categories
Funding
- Pfizer
- Lilly
- Boehringer
- Danish Cancer Society [DP07091]
- Danish National Research Foundation (Danish-Chinese Centre for Proteases and Cancer)
- Danish Ministry of Science, Technology and Innovation
- Dansk Kraeftforsknings Fond
- Fabrikant Einar Willumsens Mindelegat
- Holger Rabitz hustrus Legat
- Else og Mogens Wedell-Wedellsborgs Fond
- Birgitte og Jorgen Rygs Legat
- Civilingenior Bent Bogh og hustru Inge Boghs Fond
- Grosserer Vald. Foersom og hustru Thyra Foersoms Fond
- Lundbeck Foundation
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Introduction: We have recently shown that the protein C4.4A is induced in early precursor lesions of pulmonary adenocarcinomas and squamous cell carcinomas. In the present study, we aimed at analyzing the impact of C4.4A on the survival of non-small cell lung cancer patients and determining whether its unexpected expression in adenocarcinomas could be attributed to a specific growth type (lepidic, acinar, papillary, micropapillary, solid). Methods: Sections from the center and periphery of the primary tumor, as well as N2-positive lymph node metastases, were stained by immunohistochemistry for C4.4A and scored semi-quantitatively for intensity and frequency of positive tumor cells. Results: C4.4A score (intensity x frequency) in the tumor center was a highly significant prognostic factor in adenocarcinomas (n = 88), both in univariate (p = 0.004; hazard ratio [95% confidence interval] = 1.44 [1.12-1.85]) and multivariate statistical analysis (p = 0.0005; hazard ratio = 1.65 [1.24-2.19]), demonstrating decreasing survival with increasing score. In contrast, C4.4A did not provide prognostic information in squamous cell carcinomas (n = 104). Pathological stage was significant in both groups. In the adenocarcinomas, C4.4A expression was clearly associated with, but a stronger prognostic factor than, solid growth. Conclusions: The present results substantiate the potential value of C4.4A as a prognostic marker in pulmonary adenocarcinomas seen earlier in a smaller, independent patient cohort. Importantly, we also show that C4.4A is a surrogate marker for adenocarcinoma solid growth. Recent data suggest that C4.4A is negatively regulated by the tumor suppressor liver kinase B1, which is inactivated in some adenocarcinomas, providing a possible link to the impact of C4.4A on the survival of these patients.
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