Introduction: Right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC) have a different biology and genomic pattern. Primary tumor location is emerging as an important prognostic factor in metastatic CC patients eligible to target therapy. In a previous work, we have reported that specific tumor-infiltrating lymphocytes (S-TILs) (CD3+, CD8+, CD45RO+) may represent a valuable prognostic tool to drive the decision making-process in stage II colon cancer (CC) disease. In this study we aim to evaluate the relationship and the prognostic impact between TILs and the anatomical subsite (RCC vs LCRC) in primary non metastatic CC, regardless the stage. Methods: We performed a retrospective analysis on 48 CC pts (17F/31M, median age 68.1 - range 52-91 years) underwent adjuvant therapy, of which 33 relapsed and 15 did not, subdivided according to the anatomical sidedness of their primary tumors. We analyzed, by immunohistochemical staining, the density of CD3+, CD8+ and CD45RO + (memory cells) in the center of the tumor (CT) and in its invasive margin (IM) within the surgical tissues samples after radical surgery, comparing them on their primary tumor location. Measurements were recorded by image analysis as the number of positive cells per tissue surface unit in square millimeters. For each marker, we identified two grading of staining, high density (HD) or low density (LD), where the cut-off was the median value observed. Kaplan-Meier analysis was applied to compare the effect of TILs, between HD and LD, on disease free survival (DFS) and overall survival (OS) in the subgroups pts of RCC and LCRC. Due to the small cohort of 48 pts we have not been able to combine the tumor stage II (N = 15) and III (N = 33) with anatomical sidedness, thus this analysis was conducted subdividing patients in 17 RCC and 31 LCRC. Results: When we stratified pts by TILs density for each specific marker (CD3+, CD8+ and CD45RO+) for the anatomical sidedness, HD TILs pts showed a trend in LCRC for a longer OS compared to RCC pts, which became statistically significant for CD45RO+ in CT (p = 0.0061). On the contrary, for the entire cohort of 48 pts no differences in OS and DFS were found between LCRC and RCC pts without stratification for TILs. DFS was significantly improved in LCRC at both IM and CT only in pts with HD CD3+. On the contrary RCC showed DFS benefit only in HD CD45RO+ at IM. OS was significantly improved in LCRC in pts showing HD CD3+ and CD45RO+ at CT. HD CD45RO+ was also significant at IM. No significant differences were observed among CD3+, CD45RO+, CD8+, HD vs LD, in RCC. Conclusion: Specific HD TILs is an important prognostic factor regardless of sidedness of CC tumour; furthermore, in our analysis, the presence of HD CD45RO+ in CT of LCRC is correlated to a better survival.

Background Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy. Methods We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation. We linked the values observed with complete response and with overall survival. We also considered the role of epidermal growth factor receptor (EGFR) expression and studied the combined effect of EGFR and ADCC. Results We observed a wide range of baseline values of ADCC. Complete response did not correlate with either ADCC or EGFR expression. However, when ADCC and EGFR were considered together using a mixed score, they significantly correlated with achieving a complete response ( p = 0.04). High baseline ADCC significantly correlated with outcome compared to low ( p = 0.03), but not in patients treated without cetuximab. Patients showing high baseline levels of both ADCC and EGFR3+ achieved the best outcome compared to the others ( p = 0.02). Conclusions In this study, patients treated with cetuximab and radiotherapy, showing high baseline of both ADCC and EGFR3+, have significant higher probability of achieving a complete response and a long overall survival compared to the others.

Background Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy. Methods We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation. We linked the values observed with complete response and with overall survival. We also considered the role of epidermal growth factor receptor (EGFR) expression and studied the combined effect of EGFR and ADCC. Results We observed a wide range of baseline values of ADCC. Complete response did not correlate with either …

Purpose Adequate biomarkers are still required to optimize therapy in patients with locally advanced head and neck squamous carcinomas (HNSCC) treated with chemoradiotherapy (CRT). Methods We updated the follow-up of 66 HNSCC patients treated with CRT we described more than 10 years ago, focusing on SNP Arg/Pro (R/P) at codon 72 and somatic mutations in TP53 and on SNP309 in the MDM2 gene. Results In wild-type TP53 cases, overall survival (OS) was longer in 72RR and less favorable in 72PP (p = 0.005); when TP53 was mutated, OS was longest in 72PP and less favorable in 72RR and 72RP (p = 0.058). Median OS was significantly shorter in patients with MDM2 SNP309 GG or GT genotypes compared with the TT genotype (p = 0.002). Conclusions TP53 SNP72 may be useful in selecting patients for CRT, but has to be related to somatic TP53 mutations. The MDM2 SNP309, easily determined in peripheral blood, might be more convenient as a predictive biomarker.

e23104 Background: TNM, stage and key biological markers, direct the choice of adjuvant chemotherapy. However, many patients behave different than expected notwithstanding the careful analysis of stage and markers to select treatment. Tumor infiltrating lymphocytes (TIL), their density and site of distribution, might explain the different outcome and offer additional information to select adjuvant treatment. Methods: We performed a case-control study based on 30 cases of CC and 30 cases of BC underwent to adjuvant therapy. Fifteen pts in each cohort relapsed and 15 did not. We analyzed the density of CD3+, CD8+ and CD45RO+ (CD45+)(memory cells) in the surgical samples after radical surgery by IHC in the center of the tumor (CT) and in its invasive margin (IM). Measurements were recorded by image analysis as the number of positive cells per tissue surface unit in square millimeters. Each cohort was then divided into two groups, high density (HD) and low density (LD). Cut-off between HD and LD was the median value observed in each cohort. DFS and OS between HD and LD were compared by Log Rank test. Results: We limit the present report to the cumulative analysis of each cohort. Colon cancer: density of CD3+, CD8+ and CD45+ in CT did not affect DFS and OS. On the contrary HD of CD3+, CD8+ and CD45+ in IM showed significant benefit in DFS compared to LD (p = 0.0003, p = 0.033 and p = 0.018 respectively). Similarly, we observed a significant gain in OS in pts with HD CD3+ and CD45+ (p = 0.011 and p = 0.049) but not CD8+ (p = 0.12) in IM. Breast Cancer: we did not observe any significant prognostic difference between HD and LD of CD3+, CD8+ and CD45+, neither in CT nor in IM. Conclusions: In our study HD CD3+, CD8+ and CD45+ in CT did not impact DFS or OS, both in CC and in BC. On the contrary HD CD3+, CD8+ and CD45+ in IM significantly improved DFS in CC. We observed a significant gain in OS in CC HD CD3+ and CD45+ in IM. All these observations suggest a more pronounced role of TIL in IM compared to CT in CC. We did not observe any relationship between prognosis and TIL in breast cancer. This might reflect the broad prognostic heterogeneity in breast cancer, probably requiring a larger sample population.

Background p16 has been indicated as a suitable surrogate biomarker of HPV infection. The prognosis of p16-positive oropharynx tumors (OTs) of squamous cell carcinoma (SCC) histology is better than that of p16-negative tumors. Methods We analyzed 209 samples of head and neck SCC to establish a predictive cutoff for p16 and determine the role of p16 positivity in OTs versus non-OTs. We compared the outcomes of tumors harboring any percentage of p16-positive cells (≥1%) with those of p16-negative OTs. We then considered 3 cutoffs (10%, 50% and 70% positive cells) to evaluate the outcome of OTs/non-OTs with similar p16 expression and p16-positive versus p16-negative tumors stratified by patient age. Results p16-negative tumors among OTs and non-OTs were 29% and 49%, respectively (p = 0.0054). The cumulative distribution showed that the positive values were located around 2 focus points: 2% and 96%. Subgroup analysis showed that only OTs occurred in young patients (aged <65 years) and that there was a ≥70% gain in survival in cases with p16-positive cells. Conclusions p16 positivity influences outcome only in young patients and OTs (p = 0.048).

e12027 Background: Many treatments are available for MBC patients (pts), and the “right” choice is commonly based on pts characteristics, hormone receptor (HR) and HER2 status, sites of disease and prior therapy. Most pts receive multiple lines. Our aim is (i) to describe proportion of pts obtaining CB with each line, and (ii) to describe the predictive role of CB at 1st line on the outcome of subsequent lines (2nd - 4th), in a “real life” setting. Methods: We retrieved medical records of pts diagnosed with MBC from 1993 to 2015 at our Institution. The first 4 lines of treatment were considered in this analysis. For each line, CB was defined as progression-free status 6 months after treatment start. CB in a subsequent line was defined as CB obtained with 2nd, 3rd or 4th line. Analysis was conducted in the whole series and in 3 subgroups: HR+HER2-, HER2+ and triple negative (TN). Results: 394 pts were included in the analysis (256 HR+HER2-, 61 HER2+, 26 TN). Median PFS at 1st line in the whole population, HR+HER2-, HER2+ and TN was 12.0, 12.8, 9.7 and 5.7 months respectively. Overall survival in the whole population, HR+HER2-, HER2+ and TN was 34.7, 35.9, 31.1 and 16.1 months respectively. In the whole population, CB was achieved in 71%, 51%, 40% and 42% in 1st, 2nd, 3rd and 4th line respectively. In the same lines, CB was achieved in 75%, 52%, 39% and 44% in HR+HER2-; 70%, 54%, 41% and 39% in HER2+; 50%, 28 %, 7% and 0 in TN. In the whole series, CB in 2nd – 4th line was obtained in 53% of pts with CB in 1st line vs 30% of pts without CB in 1st line (OR 2.67, 95%CI 1.66-4.31, p = 0.0001). Similarly, proportion of pts obtaining CB was higher in those with CB in 1st line in HR+HER2- pts (50% vs 34%, OR 1.95, 95%CI 1.07-3.56, p = 0.03), in HER2+ pts (65% vs 24%, OR 6.04, 95%CI 1.65-22.04, p = 0.0065) while the difference was not significant in TN pts (31% vs 15%, OR 2.44, 95%CI 0.36-16.54, p = 0.36). Conclusions: In MBC pts receiving multiple treatment lines, chance of CB in 2nd or later lines is higher in those who obtain CB in 1st line. However, chance of subsequent CB is not negligible even in pts without CB at 1st line, especially in HR+HER2- and HER2+ pts. Our ability of predicting the best treatment sequence remains limited.

Abstract Background: HPV16 in Head and Neck (HN) cancer is a prognostic marker for positive oropharynx tumor (OT) patients. A lot of methods for direct and indirect HPV16 detection in tissue and body fluids have been analysed. Here we sought to determine the presence of HPV16 in serum collected at diagnosis in locally advanced HN tumors and to compare serum with primary tumor. Aim: Final aim is to establish the prognostic role of genomic HPV16 detection by PCR in serum of OT and in non-oropharynx tumor (non-OT) patients and to compare sensitivity with overall survival (OS). Methods: We analyzed HPV16 status in 18 OT and 32 non-OT patients (5F/45M; median age 62, range 47-81) by qualitative PCR on genomic DNA extracted from Formalin Fixed Paraffin Embedded tissues and serum samples, using specific primer pairs for E1, E6 and L1 fragments. Pos and neg control cell lines were added at each PCR session and amplicons were visualized on 2% agarose gel. Serum and tissue DNAs were extracted using the QIAmp Blood Midi Kit according to manufacturer's protocol and by proteinase K and phenol, respectively. Overall survival was performed by Kaplan-Meier curves using SPSS version 13. Results: HPV16 positive data on primary tumors were 44.4% (N= 8) in OT and 3.1% (N= 1) in non-OT for E1, 50% (N= 9) and 21.9% (N= 7) for L1 and 61.2% (N= 11) and 53.1% (N= 17) for E6 fragments, respectively. We determined that in OT patients all the HPV16 negative tissues showed a full concordance with the corresponding serum samples, on the contrary in non-OT patients we found 5 positive serum samples with a correspondent HPV16 negative tissue (7% of discordance). Concordance in HPV16 positive samples (tissue and serum) was higher in OT, with 75% for E1 (6/8), 66.7% for L1 (6/9) and 54.5% for E6 (6/11) fragments, than in non-OT, with 0% (0/1), 14.3% (1/7) and 41.2% (7/17), respectively. Moreover, our previously data performed on 66 OT patients reported that HPV16 pos tissues (13/66) for E1 showed a higher OS than in the negative ones (p = 0.016; median OS = 161.8 in pos vs 15 months in neg). Conclusions: The high concordance between sera and tissues for E1 could enable its determination on serum as an emerging marker for prognosis in OT patients. Indeed, analysis on additional 100 serum samples is ongoing with the aim of reaching statistical significance in the correlation with OS. Moreover we are collecting sequential sera taken at different times during patients' follow up in order to study HPV16 dynamical changes relevant in HN tumors. Citation Format: Daniela Vivenza, Martino Monteverde, Nerina Denaro, Mirella Fortunato, Alberto Comino, Marco C. Merlano, Cristiana Lo Nigro. HPV16 detection by PCR in serum of HNSCC patients and comparison with primary tumour tissue. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1875. doi:10.1158/1538-7445.AM2014-1875

Chemo-radiotherapy (CRT) with cisplatin-based regimens is curative in a subset of patients with locally advanced (stage III and IV) squamous carcinomas of the head and neck (LAHNSCC), but causes considerable toxicity. To seek predictive biomarkers, we analysed single nucleotide polymorphisms (SNPs) in the p53 and MDM2 genes in LAHNSCC patients treated with cisplatin-based CRT. We analysed germ-line p53 72 Arg/Pro (R/P) and MDM2 309 SNPs and somatic p53 mutational status in 140 LAHNSCC and determined their utility as predictive biomarkers. In cases with wild-type p53, overall survival (OS) was longest in 72RR (median OS = 60.8 months) and less favourable in 72PP (median OS = 6.7 months, p < 0.0001). OS in individuals with 72RP was intermediate between 72RR and 72PP, while in patients with missense p53 mutations, median OS did not reach statistical significance. Median OS was significantly shorter in patients with MDM2 309 SNP genotypes GG or GT, compared to TT (15 vs. 86 months; p < 0.0001). The predictive effect of the G allele was maintained independent of age, gender, stage, primary site, nodal status, performance status, EGFR grade, HPV status, p53 mutation and p53 SNP (HR for death 3.241; 95% CI 1.90–5.52, p < 0.001). The predictive utility of the MDM2 germ-line 309 SNP, which can be easily determined from peripheral blood, implies that it may be of value in the objective selection of patients for radical CRT. In contrast, the predictive utility of the 72 Arg/Pro SNP in p53 requires mutational analysis of p53, limiting its routine clinical use.

BackgroundTo assess the usefulness of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for differentiating the grade of malignancy of thymic epithelial neoplasm, and to determine whether 18F-FDG PET/CT can have a role in pretreatment evaluation and possibly modify treatment strategy.Materials and methodsThe data of 26 consecutive patients (14 males and 12 females) diagnosed with a thymic epithelial neoplasm were prospectively collected and analyzed retrospectively. All patients underwent standard clinical assessment and 18F-FDG PET/CT. The patients were divided into two subgroups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1) and high-risk thymoma (types B2, B3 and C). The maximum standardized uptake value (SUVmax) of the tumor, the mean SUV of mediastinum, and the tumor/mediastinum (T/M) ratio (ratio of peak SUV of the tumor to mean SUV of mediastinum) were compared to determine whether the two subgroups (low-risk versus high-risk tumors) could be distinguished by 18F-FDG PET/CT, and to test for possible correlations between 18F-FDG uptake and disease stage.ResultsThere was a strong statistical correlation between SUVmax and patient subgroup and between SUVmax and disease stage, and an even stronger correlation between SUVmax and patient subgroup and the T/M ratio; a T/M ratio of 2.75 emerged as the cut-off value for differentiating between low-risk and high-risk thymomas.Conclusions18F-FDG PET/CT can be used a “metabolic biopsy” to divide thymic epithelial neoplasm into two subgroups of high and low risk and is useful in pretreatment staging.

Despite improved outcome, optimal protocols of combined modality treatments have not been identified in advanced Head and Neck squamous cell carcinoma (HNSCC). Nor has it been established which subgroup of patients will benefit from integrated treatments. Because of the significant treatment-related toxicity, it is critical to design treatments according to molecular predictors in order to maximise therapeutic anti-tumour effect and minimise toxicity. We have investigated the potential utility of candidate predictive biomarkers in a large, homogenous cohort of patients treated in our centre. One-hundred-eighty-three paraffin-embedded specimens were obtained from 160 patients (136 males and 24 females, median age 0 58 years) with stage III-IV, locally advanced, unresectable HNSCC collected at S. Croce General Hospital since1999. All patients were treated with radical, cisplatin-based, chemo-radiotherapy regimens. P53 mutations in exons 4-10, polymorphism P72R in p53 gene and MDM2 single nucleotide polymorphism (SNP) 309 were analysed by sequencing and pyrosequencing. EGFR expression and HPV status were determined by ICH. Methylation in the CpG island of Dab-2 and DUPS2 was analyzed both by MSP and pyrosequencing. We previously showed that a functional SNP in the apoptosis signalling domain of p53 influences clinical response of HNSCC to chemotherapy. We now have investigated the hypothesis that, in addition to molecular genetic determinants, methylation profiling can identify distinct subtypes of HNSCC. p53 mutations were found in 48.5% of samples. Distribution of alleles at codon 72 in p53 was as follows: RR = 50%, RP = 40%, PP = 10%. Distribution of alleles MDM2 SNP309 was: TT =35%, TG = 43%, GG = 22%. Methylation in the Dab-2 and DUPS2 CpG islands was present in 35% and 31%, respectively. We are currently correlating these data with objective response rate, progression-free survival and overall survival. The final statistical analysis will be presented. We report the incidence of mutations, SNPs and epigenetic profiling in specific genes in HNSCC. We shall identify correlations with clinical outcome parameters. The project was partially supported by AIRC grant to M.G. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3873. doi:10.1158/1538-7445.AM2011-3873

BACKGROUND:In the last years a trend towards proximalization of colorectal carcinomas (CRC) has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP) to establish the presence of proximalization and to assess the potential predictors.METHODS:We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006.RESULTS:Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001) to 30.0% (2002-2006). Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58). The proximal ADP proportion increased from 19.2% (1997-2001) to 26.0% (2002-2006) (OR: 1.43; 95% CI: 1.17-1.89). The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17). Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16). The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46). Adjusting for these factors, the difference between the two periods was no longer significant.CONCLUSIONS:CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.

Background: Overexpression of epidermal growth factor receptor (EGFR) is related to poor prognosis in patients with head and neck cancer (HNC) treated with surgery or radiotherapy. We assessed the relationship between EGFR status and outcome in patients treated with concurrent chemoradiotherapy. Patients and Methods: Among 149 patients with unresectable HNC treated with chemoradiotherapy, immunohistochemistry was performed on 122 available tumor specimens. The following factors were included in the analysis: age at diagnosis, gender, performance status, site of primary tumor, T- and N-stage, grading, pretreatment, treatment protocol and EGFR staining. Results: Overall, 431122 (35%) were considered positive. At a median follow-up of 45 months, 5-year survival did not differ between positive and negative cases (42.1% vs. 48.0% respectively: hazard ratio for death 1.23; 95% confidence interval 0.70 to 2.17, p=0.45) nor was 5-year progression-free survival and 5-year locoregional control. Only when a smaller subgroup of tumors showing the strongest EGFR expression was considered, was any difference in 5-year overall survival detected (33.6% vs. 50.1%, p=0.009). Conclusion: EGFR appears to have no prognostic value when chemoradiotherapy is used. Possibly a small subgroup of cases with stronger positivity and worse prognosis can be identified.

Current palliative chemotherapy (CT) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers, and long-term survivals are anecdotical. Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism, DNA repair and drug resistance can explain the observed individual differences in response to drugs, in survival and in different susceptibility to the toxic effects of CT. The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen. We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer, treated with CT and alive, disease-free, at 66-82 months. Four patients with typical clinical outcome represented the control group. Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance, DNA repair, cell cycle regulation and growth factors signalling. Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response. Expression analysis in long-term survivors revealed a significant upregulation of PTEN, TP63, GADD45a and MAPK1 genes. We found also an upregulation of CYP1A1, CYP3A4 and ERBB4 genes. EGF was found to be down-regulated in long-term survivors. ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients. The present study shed light on a set of genes, which could have a predictive role in survival of patients with metastatic gastric tumors.

An incidental diagnosis of pulmonary angiosarcoma was made after surgical exploration for repeated episodes of bleeding in an 85-year-old woman. Spontaneous hemothorax is uncommon and deserves detailed investigation.

Proximalisation of colon carcinoma has been reported in many long-term studies published during the past years. There are two clinical implications: proximal tumors have a better prognosis due to the high percentage of lesions positive for microsatellite instability, and topography must be considered when stratifying patients eligible for adjuvant chemotherapy. The incidence of colorectal carcinoma grew in Italy from 44.2 to 60 new cases/1000000 per year between 1997 and 2005. This study was conducted to determine whether the site distribution of colorectal carcinoma in Italy had varied over a ten-year period, and, if so, whether the change was influenced by age and sex, as in the literature. Surgical registries and colonscopies findings, carried out between 1997 and 2006 at Cuneo's Santa Croce and Carle General Hospital, were examined. Diagnoses of carcinoma were only included if the histology was known. Following data were recorded: age, sex, date of examination, nature and location of lesions. Following anatomical segments were considered separately: rectum, sigmoid colon, descending colon, left colic flexure, transverse colon, right colic flexure, ascending colon and cecum. They were described as proximal (between the cecum and the left colic flexure) and distal (descending colon, sigmoid and rectum). Number of examinations per year per each site and number of lesions observed was calculated. Data were grouped into two five-yearsperiods for practical purposes and compared with the chi square test.1.088 surgical resections (79.9%) and 273 colonscopies (20.1%) were included in the study. 57.8% of all patients were men and 42.2% were women; median age in general population was 70.6 years (range 25th-75th centil: 62-77), 68.9 years (range 25th-75th centil: 62-76) in men and 70.3 years (range 25th-75th centil: 63-79) in women. Proximal carcinomas moved from 25.9% in 1997-2001 to 30.0% in 2002-06 (p = 0.12). No significant differences emerged from a multivariate analysis by sex and age. We can suppose that the proximalisation of carcinoma has not yet appeared in Italy. We are now performing a study to verify the proximalisation of colorectal polyps. Considering that the polyp to carcinoma sequence needs 5 to 10 years to complete, if the proximalisation of polyps will be proved, we can expect a rise in the incidence of proximal colon carcinoma in the next years, as well as we can suppose that the diagnosis and removal of proximal polyps could impede the proximalisation of colon carcinoma.