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

Cancer. 1999 Oct 1;86(7):1174-81. doi: 10.1002/(sici)1097-0142(19991001)86:7<1174::aid-cncr11>;2-8.


Background: To the authors' knowledge the prognosis of patients with intrapulmonary metastases (PM) of nonsmall cell lung carcinoma (NSCLC) has not yet been clarified fully and little is known regarding the characteristic changes that occur during the metastatic process, nor of their clinical significance.

Methods: Formalin fixed and paraffin embedded material of primary and metastatic lesions resected from 34 patients with PM of NSCLC were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44 and 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 the metastatic site (88.2%) also showed a significantly poorer prognosis than those not expressing PCNA (P = 0. 036). Patients with squamous cell carcinoma expressed CD44 variant exon 6 (CD44v6) at a significantly higher rate than adenocarcinoma patients (P = 0.0164), but expression of CD44v6 was not a significant prognostic factor. Concordance of PCNA and CD44v6 expression between the primary and corresponding metastatic sites was observed in 65% of patients (22 of 34 patients) but no difference in prognosis was observed in relation to this concordance. Cox multivariate analyses indicated that expression of PCNA was a significant prognostic indicator for both primary and 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.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Hyaluronan Receptors / analysis*
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Proliferating Cell Nuclear Antigen / analysis*
  • Protein Isoforms / analysis
  • Survival Rate


  • Hyaluronan Receptors
  • Proliferating Cell Nuclear Antigen
  • Protein Isoforms