Papillary Renal Cell Carcinoma is Associated with PTEN Hamartoma Tumor Syndrome

Overview

Journal Urology

Specialty Urology

Date 2012 Mar 3

PMID 22381246

Citations 21

Authors

Jessica L Mester

Ming Zhou

Nichole Prescott

Charis Eng

Affiliations

Soon will be listed here.

Abstract

Objective: To formally study the prevalence and histologic classification of renal cell carcinoma (RCC) in a series of patients with PTEN hamartoma tumor syndrome (PHTS).

Methods: We evaluated prevalence of RCC within a prospectively-accrued series of 219 patients found to have pathogenic germline PTEN mutations. Clinical data including pathology reports were requested for all participants. Slides and tumor blocks were requested for central pathology re-review and immunohistochemistry (IHC) analysis.

Results: Nine patients were identified with RCC. Based on Surveillance Epidemiology and End Results (SEER) data 0.28 RCC cases were expected for the group, giving an overall age-adjusted Standardized Incidence Ratio (SIR) of 31.7 (95% CI 15.4-58.1, P < 0.001) with a higher sex-adjusted SIR for females (46.7 vs 21.6 for males). Reported histology of each mutation positive patient's RCC was variable. However, on central pathology re-review of eight patients, six examined lesions were determined to be of papillary subhistology (pRCC), with the other two patients' tumors consistent with the initial report of chromophobe RCC (chRCC). IHC demonstrated complete loss of PTEN protein in all PTEN mutation positive patients' pRCCs and patchy positivity in one chRCC.

Conclusion: PHTS is a hereditary syndrome newly associated with pRCC, and PTEN IHC may be a helpful screening tool to identify pRCC patients with PHTS. Physicians caring for PHTS patients should note the >31-fold increased risk for RCC and have a low threshold for investigating possible RCC in patients with relevant complaints. Renal ultrasound is not sensitive for detecting pRCC and so PHTS patients should have alternate renal imaging (CT or MRI).

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References

Bennett K, Mester J, Eng C . Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. JAMA. 2010; 304(24):2724-31. PMC: 3655326. DOI: 10.1001/jama.2010.1877. View

Guo S, Ma F . Expression and significance of a new tumor suppression gene PTEN in primary renal cell carcinoma. Ai Zheng. 2002; 21(6):582-7. View

Marsh D, Kum J, Lunetta K, Bennett M, GORLIN R, Ahmed S . PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet. 1999; 8(8):1461-72. DOI: 10.1093/hmg/8.8.1461. View

Saslow D, Boetes C, Burke W, Harms S, Leach M, Lehman C . American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007; 57(2):75-89. DOI: 10.3322/canjclin.57.2.75. View

Hara S, Oya M, Mizuno R, Horiguchi A, Marumo K, Murai M . Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor. Ann Oncol. 2005; 16(6):928-33. DOI: 10.1093/annonc/mdi182. View

Capitan Canadas L, Salinas Sanchez J, Martinez Castillo S, Labrot Moleon I, Duran Moreno D, Sanchez Lopez D . Multiple oral fibropapillomatosis as an initial manifestation of Cowden Syndrome. Case report. Med Oral Patol Oral Cir Bucal. 2006; 11(4):E319-24. View

Choyke P, Walther M, Glenn G, Wagner J, Venzon D, Lubensky I . Imaging features of hereditary papillary renal cancers. J Comput Assist Tomogr. 1997; 21(5):737-41. DOI: 10.1097/00004728-199709000-00014. View

Chung J, Eng C . Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res. 2005; 65(18):8096-100. DOI: 10.1158/0008-5472.CAN-05-1888. View

Smith R, Cokkinides V, Eyre H . American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006; 56(1):11-25. DOI: 10.3322/canjclin.56.1.11. View

10.

Kovacs G, Akhtar M, Beckwith B, Bugert P, Cooper C, Delahunt B . The Heidelberg classification of renal cell tumours. J Pathol. 1997; 183(2):131-3. DOI: 10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G. View

11.

Lee J, Kim H, Kim Y, Lee M, Park C . Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth. J Surg Oncol. 2003; 84(3):166-72. DOI: 10.1002/jso.10302. View

12.

Lynch H, Fusaro R, Lynch J . Hereditary cancer in adults. Cancer Detect Prev. 1995; 19(3):219-33. View

13.

. Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, Adopted on February 20, 1996. J Clin Oncol. 1996; 14(5):1730-6; discussion 1737-40. DOI: 10.1200/JCO.1996.14.5.1730. View

14.

Wang K, Weinrach D, Luan C, Han M, Lin F, Teh B . Renal papillary adenoma--a putative precursor of papillary renal cell carcinoma. Hum Pathol. 2006; 38(2):239-46. DOI: 10.1016/j.humpath.2006.07.016. View

15.

Tan M, Mester J, Peterson C, Yang Y, Chen J, Rybicki L . A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011; 88(1):42-56. PMC: 3014373. DOI: 10.1016/j.ajhg.2010.11.013. View

16.

Lynch E, Ostermeyer E, Lee M, Arena J, Ji H, Dann J . Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet. 1997; 61(6):1254-60. PMC: 1716102. DOI: 10.1086/301639. View

17.

Shen-Li H, Koujak S, Szablocs M, Parsons R . Reduction of Pten dose leads to neoplastic development in multiple organs of Pten (shRNA) mice. Cancer Biol Ther. 2010; 10(11):1194-200. PMC: 3018670. DOI: 10.4161/cbt.10.11.13814. View

18.

Pilarski R, Eng C . Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet. 2004; 41(5):323-6. PMC: 1735782. DOI: 10.1136/jmg.2004.018036. View

19.

Brenner W, Farber G, Herget T, Lehr H, Hengstler J, Thuroff J . Loss of tumor suppressor protein PTEN during renal carcinogenesis. Int J Cancer. 2002; 99(1):53-7. DOI: 10.1002/ijc.10303. View

20.

Tan M, Mester J, Ngeow J, Rybicki L, Orloff M, Eng C . Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012; 18(2):400-7. PMC: 3261579. DOI: 10.1158/1078-0432.CCR-11-2283. View