Parathyroid Hormone-Related Peptide and Parathyroid Hormone-Related Peptide Receptor Type 1 Expression in Human Lung Adenocarcinoma

Background: In many primary tumors, parathyroid hormone-related peptide (PTHrP) and PTHrP type 1 receptor (PTH1R) are coex-pressed, supporting the possibility that PTHrP/PTH1R system can mediate important signals for tumor progression through paracrine/autocrine mechanisms. In non-small cell lung carcinoma the clinical relevance of the expression of PTH1R remains to be investigated. Methods: Fifty-four lung adenocarcinomas of mixed histologic type from patients with stage I and II cancer were assayed by quantitative immunohistochemistry for the expression of PTHrP and PTH1R. Results: PTHrP and PTH1R were expressed in a wide range of intensity in the cytoplasm of tumor cells, and their values showed a positive correlation. PTH1R, but not PTHrP, was expressed by plasma cells infiltrating the tumor stroma. PTHrP and PTH1R were not associated with age, tumor diameter, or histopathologic grading, whereas they were directly associated with lymph node involvement at presentation. Cox regression analysis, using PTHrP and PTH1R as continuous covariates, showed that the covariate levels were directly associated with the risk of death and metastasis. Patients whose tumors coexpressed high levels of PTHrP and PTH1R showed the highest risk of metastasis (relative risk, 5.89; 95% CI, 2.1-16.6; P = .0003) and death (relative risk, 6.24; 95% CI, 1.6-23.9; P = .0033). The presence of PTH1R-positive plasma cells in the tumor stroma was associated with a more favorable survival rate independently from the PTHrP status of the tumor. Conclusion: The paracrine/autocrine signaling through PTHrP/PTH1R could be important in early-stage lung adenocarcinoma progression. CHEST 2010; 137(4):898-908