Department of Histology, Università Cattolica del S. Cuore, Largo F. Vito 1, 00168 Roma, Italy.
Chest. 2010 Apr;137(4):898-908. doi: 10.1378/chest.09-1358. Epub 2009 Dec 1.
In many primary tumors, parathyroid hormone-related peptide (PTHrP) and PTHrP type 1 receptor (PTH1R) are coexpressed, 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.
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.
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.
The paracrine/autocrine signaling through PTHrP/PTH1R could be important in early-stage lung adenocarcinoma progression.
在许多原发性肿瘤中，甲状旁腺激素相关肽（PTHrP）和 PTHrP 型 1 受体（PTH1R）共同表达，这支持了 PTHrP/PTH1R 系统通过旁分泌/自分泌机制为肿瘤进展传递重要信号的可能性。在非小细胞肺癌中，PTH1R 的表达的临床相关性仍有待研究。
对 54 例 I 期和 II 期癌症患者的混合组织学类型肺腺癌进行定量免疫组织化学分析，检测 PTHrP 和 PTH1R 的表达。
PTHrP 和 PTH1R 在肿瘤细胞的细胞质中呈广泛强度表达，其值呈正相关。PTH1R，但不是 PTHrP，由浸润肿瘤基质的浆细胞表达。PTHrP 和 PTH1R 与年龄、肿瘤直径或组织病理学分级无关，而是与首发时的淋巴结受累直接相关。使用 PTHrP 和 PTH1R 作为连续协变量的 Cox 回归分析显示，协变量水平与死亡和转移的风险直接相关。肿瘤共同表达高水平 PTHrP 和 PTH1R 的患者具有最高的转移风险（相对风险，5.89；95%CI，2.1-16.6；P =.0003）和死亡风险（相对风险，6.24；95%CI，1.6-23.9；P =.0033）。肿瘤基质中存在 PTH1R 阳性浆细胞与 PTHrP 肿瘤状态无关，与更有利的生存率独立相关。
PTHrP/PTH1R 的旁分泌/自分泌信号可能在早期肺腺癌进展中起重要作用。
