New and old Hereditary Syndromes: Diagnosis, Genetics and molecular changes of kidney and prostate cancer

Maria J Merino MD

PRIMARY RESEARCH AREAS

1- Inherited and Sporadic Renal Cell Carcinoma

Understanding the genes that cause renal cell carcinoma
-

Clear cell

-Papillary type 1 -Hybrid/Chromophobe

-HLRCC -Oncocytoma

SDHB
MES ??, CDC ?, clear cell

2- Prostatic Cancer
A Step towards Personalized Pathology: Use of a Patient-Specific MRI-based Prostate Mold for Validation of Multi-parametric MRI in Localization of Prostate Ca

Primary Research Area(s)

Expertise:
-Morphological evaluation of benign, pre-neoplastic, and malignant renal tumors, to provide diagnosis and guidance for genetic testing. -Molecular analysis of Pre-Neoplastic lesions in renal tumors -Morphological evaluation of prostatic lesions -Identification of microRNAs in low and high grade prostatic cancer. - Identification of new biomarkers for diagnosis

TECHNOLOGIES;
Light microscopy Immunohistochemistry Chromogenic In Situ Hybridization Molecular techniques Proteomics Animal models tissue evaluation

1- Identification of Genes
-

Results
-

von Hippel-Lindau3p

Hereditary Pap RCC ..7

- Birt Hogg Dube.17p -HLRCC.1q

-Familial oncocytoma..?? - SDHB

Other??
The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Merino MJ, et al . Am J Surg Pathol. 2007.

2- New Therapies

3-Longer survival
Early detection = early therapy

Research Implications
Kidney cancer incidence continues to increase world wide with 64,770 newly diagnosed cases and 14,570 deaths. World wide problem. Need to identify specific genetic changes for identification and screening of affected family members and early treatment. Need to identify new markers for either early detection or determination of disease progression Need to develop new molecular targets for treatment of both, kidney and prostate cancer Prostate cancer will cause more than 33,000 deaths per year. With the new techniques, detection of prostate cancer has improved significantly. New forms of prostate cancer treatment (HIFU) have been developed.

Future Direction
Where do you see your research going in the next 5-10 years?
Continue to fulfill the Mission of the laboratory providing Diagnostic expertise and teaching both, intra and extramural. Continue the research in Hereditary and sporadic Renal cancer. We have families with renal tumors that have unidentified genes. - Search for tumor markers in kidney and prostate cancer by means of proteomics and Metabolomics. - Hereditary prostate cancer - The role of vaccines in prostate cancer.

What are the current challenges & obstacles? -Difficulty in getting material from other institutions -Some routine molecular markers are not available -Genetic and molecular testing is expensive

Collaborators
INTRAMURAL
Laboratory of Pathology David Roberts Mike Emmert Buck Mark Raffeld -Richard Lee -Svetlana Pack -Zied Abdullaev Urologic Oncology Branch Marston Linehan Peter Pinto Piyush Agarwal Adam Metwali -Ramaprasad Srinivasa NCI Peter Choyke Baris Turkbey James Gulley Paul Meltzer Keith Killian

- Extramural:
Victor Reuter, MSKCC Julian Sanz. University of Madrid Carmen Garcia. Cancer Center. Spain