Targeting c-KIT, PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit.

AIMS: In view of available targeted therapies, we investigated the presence of c-kit, PDGFR gene mutations and protein expression in cancer of unknown primary (CUP) in order to study their contribution in pathogenesis, their prognostic value and potential as therapeutic targets. METHODS: Mutations in hot spots c-kit exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour samples from 50 patients with CUP by means of PCR-based single-strand conformational polymorphism and protein expression by means of streptavidin-biotin immunoperoxidase assays. Molecular markers were screened for possible correlations with patient outcome. RESULTS: No shifted band was detected in any of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11 and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours revealed positive membranous CD117 expression in 30 samples (81%) of which five exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did not correlate with the clinical outcome of the patients in our cohort. CONCLUSIONS: In a moderate-sized CUP patient cohort, KIT or PDGFRa protein overexpression is rare, does not have gross prognostic significance for survival and is not associated with presence of activating mutations.

Prostate cancer epidemiology in a rural area of North Western Greece.

Epirus is a rural area of North-Western Greece. We reviewed data from 4 hospitals for 4.975 patients who underwent prostate biopsy in Epirus in the twelve year period from 1999 to 2010. Two six-year periods were compared (1999-2004 and 2004-2010). All cases of prostate cancer confirmed by biopsy were recorded and age-standardized incidence rates per 100,000 males were calculated. We also recorded the clinical stage for patients diagnosed in our hospital and correlated this with PSA and Gleason scores. Percentage of positive prostate biopsies was also calculated. There were a total of 1714 new cases during 1999-2010 and the mean annual age-adjusted incidence was 34/100,000. The mean incidences during 1999-2004 and 2005-2010 were 26/100,000 and 42/100,000, respectively. The mean age at diagnosis was 74. The most common Gleason score was 6 and the prevalent clinical stage was T2. Median PSA at diagnosis was 10.8 ng/ml. There was a significant difference between stage cT4 and all other stages regarding PSA value (p=0.000). A positive correlation was found between Gleason score and PSA (p=0.013). These results are in accordance with the incidence rise recorded in neighboring countries of South-East Europe. However we should keep in mind the risk of overdiagnosis and the detection of low-risk cancers that would not have caused morbidity or death during a man's lifetime anyway.