Optimized immunohistochemistry using the D5F3 antibody provides a reliable test for identification of ALK-positive lung adenocarcinomas.

We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative. The FISH positive/IHC-positive cases with moderately intense reactivity had the typical clinicopathologic features of ALK-positive patients (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01; cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas. Inclusion of this information in the pathology report at the time of the histological diagnosis might significantly shorten time to treatment.

Left-sided early onset colorectal carcinomas: A sporadic neoplasm with aggressive behavior.

BACKGROUND: Early onset (≤50y) colorectal carcinomas (EO-CRCs) are increasing in incidence according to epidemiological data. We investigated clinical-pathological, molecular features and outcomes of 62 left sided EO-CRCs (EOLS-CRCs) and compared them to a group of late onset (≥65) LS-CRCs (LOLS-CRCs). MATERIALS AND METHODS: Samples were evaluated for pathological features and microsatellite instability (MSI). Overall survival (OS), disease free survival (DFS) and disease specific survival were evaluated in both groups. RESULTS: Five out 62 (8%) EOLS-CRCs showed MSI phenotype. Interestingly these cases were aged 26-39y. Most EOLS-CRCs present at advanced stage and this was statistically significant when compared to LOLS-CRCs. OS was better in EOLS-CRCs whilst DFS showed a worst profile in EOLS-CRCs either in low and high stages even though young patients were treated more often with adjuvant chemotherapy compared to older ones at the same disease stage. CONCLUSIONS: Most EOLS-CRCs are sporadic non Lynch, microsatellite stable (MSS) CRCs. Our data show that when compared with LOLS-CRCs the early group represents an aggressive disease with worst outcome underlining a possible different carcinogenic pathway.

Tumor regression grades, K-RAS mutational profile and c-MET in colorectal liver metastases.

INTRODUCTION: Recently TRG, necrosis grade and the rate of viable cancer cells of colorectal liver metastases were correlated with the response to chemotherapy treatments, whereas K-RAS mutations and c-MET over-expression were correlated with the prognosis. METHODS: 58 resection specimens were assessed for regression grades. Patients undergone neo-adjuvant treatments were compared to patients who underwent therapy exclusively adjuvantly. We investigated the K-RAS mutational profile, the c-MET over-expression along with patients' survivals curves. RESULTS: Patients undergone neo-adjuvant treatment presented significant higher fibrosis rates and lower rates of viable cells. 36.7% of the patients had a K-RAS mutation and the 26.7% presented c-MET over-expression, but these features did not correlate with patients' clinical/pathological data. Survival analysis documented that K-RAS WT patients presenting c-MET over-expression had worse outcomes. CONCLUSION: Fibrosis and the rate of viable cells significantly correlate with the response to chemotherapy treatments. c-MET is a promising marker in K-RAS WT patients.

A Case of Sinonasal Melanoma With Unusual Primary Exon 17 KIT D820G Mutation.

Sinonasal melanomas are rare neoplasms with poor prognosis that may harbor KIT and NRAS genes mutations. Molecular alterations represent possible targets of tailored therapeutic approaches. We describe the case of a 74-year-old patient with primary melanoma of the nasal cavity. Mutational analysis of KIT demonstrated a point missense mutation D820G in exon 17. This represents, to our knowledge, the first case of sinonasal melanoma harboring this specific KIT mutation. Although KIT mutations confer sensibility to thyrosine-kinase inhibitor, it has been proved that this is strongly dependent on the region in which this alteration occurs. Thus it seems very important to perform an accurate gene mutational analysis to provide a biological rationale to the tailored therapy.

High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults.

OBJECTIVES: To investigate prevalence and age-distribution of ALK- or ROS1-translocated adenocarcinomas in patients ≤50 years of age. MATERIALS AND METHODS: Paraffin sections of pulmonary adenocarcinoma were analyzed for ALK (637 cases) and ROS1 (376 cases) translocations using FISH, and for EGFR mutations (789 cases) using mutant-specific Real-Time PCR. RESULTS: ALK or ROS1 fusions were detected in 55 of 637 cases (8.6%). When patients were stratified for age, it was found that six of six cases (100%) of lung adenocarcinoma diagnosed in patients <30 years of age were translocated for ALK (4 cases) or ROS1 (2 cases). With the increase of age, there was a gradual decrease in the percentage of positive cases. In fact, ALK-translocated or ROS1-translocated cases were 5 of 17 cases (29%) in the 31-40 years age-group, 6 of 46 cases (13%) in the 41-50 years age-group, and 38 of 568 cases (7.0%) in patients older than 50 years. The six patients <30 years of age (5F/1M), including two pediatric patients (≤18 years old), presented with stage IV disease, were never or light smoker, and had no family history of pulmonary tumours. Four of the six patients, were treated with crizotinib and had an objective response. CONCLUSIONS: Our findings provide evidence that ALK or ROS1 translocations are crucial events in tumourigenesis of pulmonary adenocarcinoma of very young patients, including pediatric patients.