We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N2) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1a, PI3K, pAKT, pmTOR, moesin, P21, 4 E BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1a, PI3K, claudin-1, AF6 and pAKT in N2 BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N2 patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N2 BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N2 patients with favorable prognosis.Widespread screening programs in western countries have significantly improved early detection of breast carcinoma (BrCa) resulting in an increased incidence of early stages of tumors. Furthermore, significant improvements in management of node negative (NÀ) patients have resulted in longer survival and better quality of life after therapy. It is widely acknowledged that NÀ BrCa may now tend to have a fairly good overall survival rate since only 30-40% of patients develop distant metastases.1 According to current guidelines and since there are no means of clearly identifying patients who will not relapse, hence should not receive adjuvant chemotherapy, most patients are offered chemotherapy leading to overtreatment of a large proportion.2,3 Clearly, markers permitting the identification of patients not requiring aggressive adjuvant therapy are urgently needed to avoid unnecessary exposure of women to the potential toxicity of such treatments, and also to reduce the overall cost of BrCa management.

Background:The amplification of epidermal growth factor receptor (EGFR) in triple negative breast carcinomas (TNBC) suggests its potential therapeutic application, as for HER-2, using standardised methods of measurement. In this regard, we aimed to compare several methods for evaluating EGFR amplification along with potential mutations for suitability in clinical practice.Methods:Tissue sections of 138 TNBCs were used (1) to compare EGFR amplification and expression by silver in situ hybridisation (SISH) to qPCR and immunohistochemistry (IHC) and (2) to search for EGFR mutations, along with Kras, PI3K, Braf and HER-2 mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation.Results:(1) Amplification of EGFR was observed in well-characterised TNBCs (up to 92%); (2) qPCR correlated with SISH with 94% specificity and 75.6% sensitivity; (3) IHC correlated with SISH with 97% sensitivity and 78% specificity; (4) no EGFR, Kras mutations or EML4-ALK translocations were found, but PI3K and Braf mutations were observed in 26% of cases; and (5) small, acentric circular extrachromosomal DNA similar to ‘double minutes' in glioblastomas was observed in 18% of SISH sections.Conclusions:SISH and IHC are methods that are suitable in clinical practice to screen for EGFR amplification and overexpression, which are frequently observed in TNBC. Patients with TNBC are potential candidates for EGFR-targeted therapy combined with PI3K and Braf inhibitors.

BackgroundMesenteric panniculitis is a rare chronic fibrosing inflammatory disease that typically affects the adipose tissue and mesentery of the small intestine but may also affect the mesosigmoid and the mesocolon. The pathology of this disease remains unclear despite association with some malignancies or inflammatory disorders. We report a case of mesocolic panniculitis and a literature review of its clinical presentation, imaging findings, associated conditions and treatment options.Case presentationA 64 year-old Caucasian man was admitted to the gastroenterology department for severe weakness, left lower quadrant abdominal pain, weight loss and diarrhoea. Physical examination revealed a palpable firm mass occupying the entire left part of the abdomen. Abdominal CT-scan showed fatty infiltration of the mesosigmoid and left mesocolic fat which was strongly suggestive of panniculitis. Laparoscopic surgery revealed an inflamed and edematous mesocolon and mesosigmoid; the sigmoid mucosa appeared petechial which was suggestive of venous ischemia. Histological examination of surgical biopsies revealed mesocolic panniculitis. Despite exhaustive investigation, no associated conditions were found and the cause was classified as idiopathic. Surprisingly, the patient clinically improved without therapeutic intervention other than supportive care.ConclusionAlthough mesenteric panniculitis is most often a radiographic diagnosis without clinical symptomatology, it can also present with significant general status alteration. We report a case of mesocolic panniculitis complicated by development of an inflammatory mass associated with ischemic colitis. Mesenteric panniculitis is a difficult diagnosis to make which typically requires histologic confirmation. The overall prognosis is good with supportive treatment.

To date, vaginal/cervical clear cell adenocarcinoma (CCAC) has not been reported in the granddaughters of women treated with diethylstilbestrol (DES) during pregnancy. We present an 8-year-old girl with a history of severe vaginal bleeding who was diagnosed with cervical CCAC. She underwent fertility-sparing surgery and radiotherapy. No sign of recurrence was detected throughout a 10-year follow-up. Her grandmother had received DES therapy during pregnancy with the patient’s mother. Although no direct causal link is demonstrated, this case raises for the first time, the hypothesis of multigenerational effects of DES in girls and strongly suggests the need to follow the granddaughters of DES-treated women.