J Korean Med Sci.  2007 Apr;22(2):318-325. 10.3346/jkms.2007.22.2.318.

Immunohistochemical Analysis of Non-Small Cell Lung Cancer: Correlation with Clinical Parameters and Prognosis

• Yoo J
• Jung JH
• Lee MA
• Seo KJ
• Shim BY
• Kim SH
• Cho DG
• Ahn MI
• Kim CH
• Cho KD
• Kang SJ
• Kim HK

• KMID: 1713194
• DOI: http://doi.org/10.3346/jkms.2007.22.2.318

Abstract

Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC.

Keyword

Carcinoma, Bronchogenic; Cell Cycle; Apoptosis; Angiogenesis Factor; Prognosis

MeSH Terms

Tumor Markers, Biological/*analysis
Survival Rate
Survival Analysis
Statistics
Sensitivity and Specificity
Reproducibility of Results
Prognosis
Outcome Assessment (Health Care)/*methods
Neoplasm Proteins/*analysis
Male
Lung Neoplasms/*diagnosis/*metabolism/mortality
Korea/epidemiology
Humans
Female
Carcinoma, Non-Small-Cell Lung/*diagnosis/*metabolism/mortality
Aged

Figure

• 

  Fig. 1 Immunohistochemistry for p16 (A) and bcl-2 (B), showing diffuse strong reactivity (×40).

• 

  Fig. 2 Kaplan-Meier survival plots for non-small cell lung carcinoma. (A) p16 positive (solid line) vs. negative (dotted line); (B) bcl-2 positive (solid line) vs. negative (dotted line). p-values by Mantel-Cox log-rank test were 0.071 (A) and 0.047 (B).

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