PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients.

To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy (P<0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR (P<0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity (P<0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.

Secretory changes in preovulatory endometrium during controlled ovarian hyperstimulation with buserelin acetate and human gonadotropins.

Twenty-one patients with unexplained infertility underwent controlled ovarian hyperstimulation with buserelin acetate and human menopausal and chorionic gonadotropins, and follicular growth was monitored by ultrasonography and daily 17 beta-estradiol (E2) assays. Endometrial biopsy was performed when E2 levels were greater than or equal to 250 pg/mL per follicle and the follicular diameter was greater than or equal to 17 mm. As controls, we studied 20 preovulatory endometrial biopsies from patients with a male infertility factor. The biopsy material was examined at light, scanning, and transmission electron microscopes, and a morphometric analysis was performed. Preovulatory endometrial mucosa during controlled ovarian hyperstimulation showed accentuated proliferative aspects in both the glandular and stromal components and more frequent early secretory phenomena compared with the controls. The preovulatory progesterone (P) levels observed in our study seem to exclude the possibility that such early secretory aspects of the hyperstimulated endometrium are because of higher P concentrations in patients compared with controls.

Massive renal adenomatosis: a case exhibiting low-grade malignancy.

A young man with gradually enlarging kidneys and radiographic findings strongly suggestive of polycystic disease was found on autopsy to have massive bilateral renal enlargement due to innumerable multifocal tumors, arising in atypical renal tubular epithelium, whose microscopic appearance ranged from that of so-called renal adenoma to that of low-grade renal cell carcinoma. Electron microscopy confirmed the epithelial nature of the neoplasms. Local lymph node metastases and pulmonary micrometastases were present. Death was due to renal insufficiency and to refractory hyperkalemia probably secondary to tumor necrosis. Only one similar case is reported in the recent literature.