Expression of proliferating cell nuclear antigen and CD44 variant isoformsin the primary and metastatic sites of nonsmall cell lung carcinoma with intrapulmonary metastases

BACKGROUND. To the authors' knowledge the prognosis of patients with intrap ulmonary metastases (PM) of nonsmall cell lung carcinoma (NSCLC) has not ye t been clarified fully and little is known regarding the characteristic cha nges that occur during the metastatic process, nor of their clinical signif icance. METHODS. Formalin fixed and paraffin embedded material of primary and metas tatic lesions resected from 34 patients with PM of NSCLC were stained immun ohistochemically with proliferating cell nuclear antigen (PCNA) and CD44 an d its variant isoforms. RESULTS. Patients with NSCLC expressing PCNA in the primary tumor site (79. 4%) showed a significantly poorer survival (5-year survival rate of 20.2%) compared with the 5-year survival rate of 57.1% for patients not expressing PCNA in the primary tumor site (P = 0.048). Patients expressing PCNA in th e metastatic site (88.2%) also showed a significantly poorer prognosis than those not expressing PCNA (P = 0.036). Patients with squamous cell carcino ma expressed CD44 variant exon 6 (CD44v6) at a significantly higher rate th an adenocarcinoma patients (P = 0.0164), but expression of CD44v6 was not a significant prognostic factor. Concordance of PCNA and CD44v6 expression b etween the primary and corresponding metastatic sites was observed in 65% o f patients (22 of 34 patients) but no difference in prognosis was observed in relation to this concordance. Cox multivariate analyses indicated that e xpression of PCNA was a significant prognostic indicator for both primary a nd metastatic sites (P = 0.014 and P = 0.0095, respectively). CONCLUSIONS. This study demonstrated that PCNA expression was a significant prognostic factor for both primary and metastatic lesions in PM patients. CD44v6 showed histogenesis of the tumor, but no relation with the prognosis could be ascertained. Cancer 1999;86:1174-81. (C) 1999 American Cancer Soc iety.