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DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10–30%) and of varying intensity (1 + to 2 +). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) andmyeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

17 Background: Patients diagnosed with gastroesophageal adenocarcinoma (GEA) have a poor prognosis despite curative attempts with multimodal treatment including surgery, chemotherapy (CT) and radiotherapy (RT). VEGF, EpCAM, MUC1, CK19 and CK20 and CD133 have shown to provide additional prognostic information in advanced GEA patients. Methods: Circulating mRNA of total VEGF (and 2 VEGF isoforms 121 and 165), EpCAM, MUC1 and CD133 were determined in 36 loco-regional GEA patients (pts). Blood samples were collected before surgery or, when indicated, before the preoperative chemotherapy treatment, within a 7 days window. Additionally, 14 healthy volunteers and 7 advanced GEA pts were included to comparative analyses. The Wilcoxon test was used to assess differences in expression among the groups. Results: Pre-surgery CT was administered in 30 pts (79%). ECF or its modifications were administered in 22 pts, and FOLFOX in 7 pts. Type of resection achieved was R0 (19 pts, 59%), R1(7 pts, 22%) and R2 (6 pts, 10%). Post-surgery CT was administered in 22 pts (73%) including ECF or its modifications (10 pts), FOLFOX (7 pts) and CT-RT (4 pts). PFS occurred in 19 pts (61%) and 34 patients remained alive at the time of this analysis. Patients diagnosed with loco-regional GEA exhibited over expression as compared to healthy volunteers of VEGFi121 in 17 pts (47%) by 33-fold median change (IQR 5-43, %, p = 0.0008); VEGFi165 in 17 pts (47%) by 15-fold (IQR 5-36, p = 0.002); total VEGF in 19 pts (53%) by 15 fold (IQR 8-59, p = 0.01); EpCAM in 8 pts (22%) by 3-fold (IQR 0.5-3, NS); MUC1 in 19 pts (53%) by 23-fold (IQR7-59, p = 0.0008); and CD133 in 2 pts (6%) by 55-fold (IQR 28-83, NS). CK20 expression was not detected in healthy controls but was detected in 3 patients. Conclusions: VEGF and its isoforms VEGF121 and VEGF165 and MUC1 are potential diagnostic biomarkers in GEA. Due to the short follow-up of patients we cannot yet evaluate their role as prognostic biomarkers.

e22073 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. In this context, tumor infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in tissue specimens and in peripheral blood are being tested as two emerging prognostic and predictive factors. We designed a protocol to analyze specifically TILs before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response. Methods: From March 2011 to January 2013, 48 patients (18 HER2+/ 30 HER2-) with T2-4 N0-3 breast carcinoma treated with neoadjuvant chemotherapy in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study protocol. CD3+, CD8+, CD8-16-56+ and Foxp3+ cell infiltrates were detected by immunohistochemistry before and after the end of neoadjuvant chemotherapy in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle of CT to determine the immunophenotype and regulatory cell profile. Cell populations were determined by flow cytometry analysis of whole blood. Results: By January 2013, 35 patients (11 HER2+/ 24 HER2-) were operated. Pathological complete responses (pCR) or near pCR (grade 4/5 Myller and Payne) were attained in 13 patients. pCR was achieved in 63.63% (7 of 11) of tumors overexpressing HER2, but in only a 25% (6 of 24) of HER2-negative tumors. Overall Tregs diminished in the pCR and non pCR groups. Disappearance of Tregs (Black grading system) was more frequent in the pCR group (69.23 vs 54.54%) and HER2+ population (63.63 vs 58.53%), although differences were not statistically significant. CD8+ infiltrates remain stable during treatment. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates with no changes in CD8+ cytotoxic lymphocytes. Changes observed in lymphocytic infiltrates during neoadjuvant treatment indicate that Tregs may represent an interesting therapeutic target in breast carcinoma.

3042 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. We designed a protocol to analyze immune ...