AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target's expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors.

Double-staining Immunohistochemistry Reveals in Malignant Pleural Mesothelioma the Coexpression of ERCC1 and RRM1 as a Frequent Biological Event Related to Poorer Survival.

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. To date, standard MPM therapy is still limited to surgery, radiotherapy, and chemotherapy, including pemetrexed and platinum compounds. The main mechanisms of platinum resistance are associated with DNA repair pathways. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) are important components of the DNA repair, considered as prognostic and predictive biomarkers in various cancer types. The main goal of the present study was to investigate the ERCC1 and RRM1 expression and their potential impact on outcome in this tumor. A series of 73 MPM, mainly treated with a platin-based regimen, was collected and the immunohistochemistry tests were performed to assess ERCC1 and RRM1 expression. In addition, a multiplex immunohistochemistry has been validated to detect simultaneously the 2 proteins on the same slide. In our series, 36 of 73 cases showed ERCC1 expression and 55 of 73 showed RRM1 expression. The double immunohistochemical staining showed the coexpression of ERCC1/RRM1 in 34 of 73 cases. A significant association between ERCC1 and RRM1 expression was observed in our series (P<0.05). Patients with ERCC1/RRM1 coexpression experienced shorter median overall survival (6.6 vs. 13.8 mo, log-rank=7688; P=0.006). Our results suggest that the coexpression of ERCC1/RRM1 could define a group of MPM patients with the worst prognosis who should need likely alternative treatment. In conclusion, we propose the putative usefulness of ERCC1/RRM1 coexpression as prognostic biomarkers for overall survival in MPM.

[Gastrointestinal stromal tumors: a rare nosological entity and a model example for the use of personalized therapy with a molecular basis]. / Tumori stromali gastrointestinali: entità nosologica rara e modello esemplare per l'utilizzo di terapie personalizzate su base molecolare.

GIST (gastrointestinal stromal tumor) are stromal tumors of the gastrointestinal tract, belonging to a category of rare tumor called soft tissue sarcoma deriving from the Cajal mesenchymal cells. GIST present a peculiar immunohistochemical profile that is indispensable for a diagnostic confirmation: approximately 80% of cases present a mutation of the c-kit gene which codifies for a trans membrane receptor (antigen CD117) at tirosin-kinasic activity whose activation triggers cell proliferation. About 7% of GIST cases present mutations in the tirosin-kinasic receptor homologous to c-kit, the PDGFRα. Recent studies show that a considerable variety exists in the molecular and genetic characteristics that guide the GIST pathogenesis, therefore allowing the identification of different molecular subtypes of GIST with different prognosis and sensitivities to the specific treatments. The presence of different subtypes in an illness that has been so recently discovered is a model for oncology. With the availability of very active and specific therapeutic agents against molecular alterations which cause the majority of cases of GIST, these tumors have become the models for personalized cancer treatments.

Intramuscular myxoma of the deltoid muscle: report of a case.

Intramuscular myxoma is a rare, benign lesion of mesenchymal origin, affecting the skeletal muscles. We report the case of a 75-year-old woman presenting with a mass of the right deltoid region. On the MRI examination it was interpreted as a lipomatous lesion. She underwent marginal excision. The pathological examination revealed the diagnosis of intramuscular myxoma.

A case of leiomyoadenomatoid tumour of uterine serosa: speculations about differential diagnosis.

Adenomatoid tumour is a benign rare lesion of the female genital tract, localised in the wall of fallopian tubes or beneath the uterine serosa. It is often accompanied by smooth muscle proliferation, obscuring the presence of adenomatoid tumour, resulting in misdiagnosis of cellular leiomyoma.Here, a case of uterine serosal adenomatoid tumour associated with multiple leiomyomas and pelvic endometriosis in a 44-year-old woman who underwent surgical removal for uterine bleeding and abdominal pain is presented.

Small bowel intussusception secondary to inflammatory fibroid polyp of the ileum: report of a case.

Inflammatory fibroid polyps are rare benign lesions of uncertain origin, that may occur in many different locations in the gastrointestinal tract, the gastric antrum being the most common site, followed by the small bowel. These lesions can cause abdominal pain, gastrointestinal bleeding, intestinal obstruction or intussusception. In the case of a gastric inflammatory fibroid polyp in the presence of Helicobacter Pylori infection, the patient can benefit from pharmacological eradication of Helicobacter Pylori. In case of an intestinal inflammatory fibroid polyp causing acute abdomen, the treatment is surgical. In this paper we report a case of an adult male patient with ileal intussusception due to an inflammatory fibroid polyp. A 62-year-old male patient presenting with acute abdomen underwent an exploratory laparotomy. At surgery an ileal tumour 15 cm from the ileocecal valve causing ileoileal intussusception was found. The intussuscepted segment was resected and an end-to-end anastomosis was carried out. The postoperative period was uneventful and the patient was discharged 5 days after the surgery. After 6 months, he is doing well and back to normal life. Even if inflammatory fibroid polyps are benign lesions, surgical treatment is the only solution when they present with intestinal intussusception. Preoperative diagnosis of inflammatory fibroid polyps is often difficult, and confirmation can only be obtained by histological and immunohistochemical examination. Since they can mimic malignant stromal lesions, the differential diagnosis must be done very carefully.