e14057 Background: MicroRNAs (miRNA), small non-coding RNA molecules act as post-transcriptional regulators of gene expression and have shown diagnostic and prognostic potential in cancer. We profiled miRNA expression in LARC patients treated with neoadjuvant CRT to assess whether a miRNA signature correlated with the degree of pathological response. Methods: FFPE-derived tumour samples from 85 LARC patients treated with preoperative CRT (45 Gy plus 5.4 Gy boost, 180-cGy daily fractions and concurrent capecitabine) were analyzed for miRNA signature generation and IHQ-EGFR protein expression. Pathological response was scored according to the Mandard’s TRG scale. Expression profile of 667 mature miRNAs obtained by TLDA Human MicroRNA Panel or individual TaqMan MicroRNA Assays were normalized using RNU48, selected as the best normalizer by Normfinder program. The correlation between miRNA expression profile and pathologic response was assessed by class-comparison, unsupervised hierarchical cluster analysis and U-Mann Whitney test. Results: A pathological complete response was achieved in 12 patients (14%), whereas no response (TRG 3-4) was observed in 49 patients (58%). As expected, TRG correlated with both relapse and disease-free survival (p<0.01). We identified a miRNA signature that correctly differentiated extreme-phenotype of responder patients (TRG-1 vs TRG-4). The top 10 of them were selected to be validated by individual Q-RT-PCR in the global series. While up-regulation of miR-21*, miR-99*, miR-125b, miR-125b1*, let-7c and miR-490 significantly correlated with a higher likelihood of achieving pathological response (TRG-1-2), miR-21 and miR-125a-3p downregulated levels were found to be associated with a TRG-4 response. High EGFR protein expression levels, determined by IHQ, were seen in the 93% of poor-responders patients (TRG-4). Interestingly, miR-21 and miR-21* levels inversely correlated with EGFR expression. Conclusions: A differential expression of miRNAs may predict the degree of pathological response to CRT in LARC patients. A miRNA-mediated role for EGFR pathway in CRT resistance warrants further research.

Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients.

No abstract

Los tumores del estroma gastrointestinal (GIST) poseen mutaciones en los genes del receptor de la tirosín quinasa (RTKs) KIT y PDGFRA. La posibilidad de bloquear esta actividad ha significado una nueva esperanza terapéutica. El diagnóstico de GIST recae en la expresión inmunohistoquímica del c-KIT, pero un 4-15% son c-KIT negativos (aún en presencia de mutación), y sin embargo estos pacientes podrían beneficiarse del tratamiento con inhibidores tirosín quinasa (TKIs).El DOG1 es un nuevo anticuerpo cuya sensibilidad y especificidad parece ser superior o igual a la del c-KIT. El objetivo de este trabajo es evaluar la sensibilidad (Se) y especificidad (Sp) de DOG1 en GIST de tipo usual (c-KIT positivos), de tipo inusual (c-KIT negativos) y frente a otros tumores fusocelulares mesenquimales, y comparar la validez diagnóstica del DOG1 frente al c-KIT.Estudiamos 40 GIST, 39 c-KIT positivos y un c-KIT negativo. Se realizó un panel inmunohistoquímico con los anticuerpos: c-KIT, CD34, actina músculo liso, DOG1 y S100, en los GIST como en siete tumores fusocelulares.La Se y Sp de GIST para DOG1 fue del 100 y 97,5% para c-KIT. La inmunoreactividad para DOG1 en todos los tumores fusocelulares fue negativa. La validez diagnóstica de DOG1 y C-KIT fue similar a la hora de detectar GIST y no GIST. DOG1 es un marcador específico y sensible para el diagnóstico y diagnóstico diferencial de GISTs (es capaz de detectar algunos GIST sin mutación en RTK). El DOG1 debería de formar parte del panel inmunohistoquímico para el diagnóstico de GIST.Palabras clave. GIST. DOG1. aBstractGatrointestinal stromal tumours (GIST) harbour oncogenic mutations in tyrosin kynases receptors (RTKs) including KIT and PDGFRA. The inhibition of this activity has been regarded as the primary target for the treatment of these patients. Diagnosis of GIST relies on c-KIT inmunoreactivity; however there is a 4-15% of GISTs that are C-KIT negative which may lead to underdiagnosis of GISTs and possible withholding of therapy.The novel gene DOG1 has been found overexpressed in GISTs and has potential as a diagnostic marker for GISTs showing even more sensitivity (Se) and specificity (Sp) than c-KIT for the diagnosis of these tumors. In this study we compared the (Se) and (Sp) of DOG1 in typical and atypical GISTs (c-KIT positive or negative) with c-KIT and other mesenchymal neoplasms in the differential diagnosis of GISTs We examined 40 GIST (39 showed inmunoreactivity for c-KIT and one was c-KIT negative) and another seven fusiform tumors. An inmunohistochemical panel was performed with c-KIT, CD34, smooth muscle actin, DOG1 and S100 antibodies on both types of neoplasms.The overall Se and Sp of DOG1 and KIT in GISTs were nearly identical: 100 and 97,5%. Negativity for DOG1 was observed in all fusiform mesenchymal neoplasms.DOG1 is highly expressed in GIST and its expression seems quite specific for these tumours when the differential diagnosis includes another mesenchymal neoplasms.DOG1 should be added to the diagnostic panel evaluating GISTs.

S u b c u t a n e o u s m e t a s t a s i s as the first m a n i f e s t a t i o n of a s o l i d -p s e u d o p a p i l l a r y t u m o r of the p a n c r e a sF. A r i a s de la Vega", M.L. G 6 m e z D o r r o n s o r o b a n d F.J. J i m 6 n e z "Services of"Radiation Ontology, ~'Pathology a n d "Radiology.