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BJU Int. 2001 Dec;88(9):960-6.

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

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1
Department of Urology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. kamait@dokkyomed.ac.jp

Abstract

OBJECTIVES:

To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival.

PATIENTS AND METHODS:

The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription.

RESULTS:

Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05).

CONCLUSIONS:

These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

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