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.

Background: Lung cancer initially manifesting as gastrointestinal (GI)-tract metastasis is exceedingly rare, representing a diagnostic challenge and a late-stage disease sign. The clinicopathologic characteristics of the largest series of lung carcinomas initially presenting with GI involvement were described, focusing on differential diagnosis and therapeutic options. Methods: Eighteen consecutive cases of lung cancer (11 surgical specimens and 7 biopsies) initially diagnosed on GI histologic samples were identified during routine pathologist practice. All cases were immunostained with thyroid transcription factor-1 (TTF-1), caudalrelated homeobox 2 (CDX2), and cytokeratins 7 (CK7) and 20 (CK20). Clinical and radiological data were obtained in all cases. Results: There were 10 women and 8 men with a mean age of 68.5 years. The small bowel was the most common GI involved site (12 cases), followed by the stomach (four) and large intestine (two). Only half of cases were correctly diagnosed on GI biopsies. Fourteen patients died shortly from disease (mean follow-up, 3 months); two are still alive with multiple metastases, and two patients with the GI tract as the unique site of metastasis underwent pulmonary lobectomy and chemotherapy and are alive without evidence of disease. At morphology, there were 10 large cell undifferentiated carcinomas and eight adenocarcinomas. All cases were immunostained for CK7 and 89% for TTF-1, whereas CK20 and CDX2 were completely negative. Conclusion: Lung cancer presenting as GI-tract metastasis is probably more frequent than expected, and pathologists should always keep in mind this possibility when dealing with undifferentiated GI carcinoma. Immunostaining with TTF-1, CDX2, CK7, and CK20 is helpful in highlighting lung primary. Although GI metastasis from lung cancer is associated with dismal outcomes, pulmonary resection coupled with chemotherapy might represent a therapeutic option in selected patients with a solitary GI-tract metastasis.

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Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome characterised by a dramatic onset requiring an urgent treatment with plasma exchange (PE). However, the prognosis is still dismal for PE related complications, a rate of failure and remarkable frequencies of relapse. TTP post transplantation is largely described as an outstanding, unusual complication of allogenic transplantation, but it is rarely mentioned after autologous transplantation. We describe a 62-year-old Caucasian patient who presented with TTP, accompanied by renal failure, after an autologous transplantation for multiple myeloma. PE together with hemodialysis was rapidly initiated but without any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal antibody,was reported to be effective, we administered four courses of Rituximab inducing a complete remission of TTP and subsequently of the renal failure. This response to Rituximab in TTP post transplantation is suggestive of a possible implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for an investigational approach in this settings.