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1.  Papillary Renal Cell Carcinoma is Associated with PTEN Hamartoma Tumor Syndrome 
Urology  2012;79(5):1187.e1-1187.e7.
To formally study the prevalence and histological classification of renal cell carcinoma (RCC) in a series of patients with PTEN Hamartoma Tumor syndrome (PHTS).
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.
Nine patients were identified with RCC. Based on 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 8 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.
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).
PMCID: PMC3341468  PMID: 22381246
PTEN germline mutations; Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome; Carcinoma, Kidney
2.  A Multi-institutional Phase II study of the efficacy and tolerability of Lapatinib in patients with advanced hepatocellular carcinomas 
Hepatocellular carcinoma (HCC) is on the rise worldwide. HCC responds poorly to chemotherapy. Lapatinib is an inhibitor of EGFR and HER2/NEU both implicated in hepatocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in HCC.
A Fleming phase II design with a single stage of 25 patients with a 90% power to exclude a true response rate of < 10% and detect a true response rate of ≥30% was utilized. The dose of lapatinib was 1,500 mg/d administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/NEU/CEP17 and status of downstream signal pathway proteins.
Twenty-six patients with HCC enrolled on this study. 19% had one prior therapy. Most common toxicities were diarrhea (73%), nausea (54%) and rash (42%). No objective responses were observed. Ten (40%) patients had stable disease (SD) as their best response including 6 (23%) with SD lasting > 120 days. Median progression-free-survival was 1.9 months and median overall survival 12.6 months. Patients who developed a rash had a borderline statistically significant longer survival. Tissue and blood specimens were available on >90% of patients. No somatic mutations in EGFR (exons 18–21) were found. In contrast to our previous findings, we did not find evidence of HER2/NEU somatic mutations. PTEN, P-AKT and P70S6K expression did not correlate with survival.
Lapatinib is well-tolerated but appears to benefit only a subgroup of patients for whom predictive molecular or clinical characteristics are not yet fully defined.
PMCID: PMC2774354  PMID: 19737952

Results 1-2 (2)