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Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Authors' Affiliations: ¹ Research, Anesthesiology, and Medicine Services, VA San Diego Healthcare System, San Diego, California and ² Departments of Anesthesiology, Pathology, Mathematics, Family and Preventative Medicine, and Medicine, University of California San Diego, La Jolla, California

Requests for reprints: Randolph H. Hastings, VA Medical Center (125), 3350 La Jolla Village Drive, San Diego, CA 92161-5085. Phone: 858-642-3437; Fax: 858-822-5009; E-mail: rhhastings{at}ucsd.edu.

Purpose: Parathyroid hormone–related protein (PTHrP) is commonly expressed in non–small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation.

Experimental Design: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates.

Results: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age.

Conclusions: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.

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