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Triple-negative breast cancer (TNBC) represents approximately 10-20% of Breast Cancer (BC) diagnosed worldwide and in accordance with the current guideline it is defined by the absence of expression of the of expression of the estrogen receptor (ER=60yThe majority of BC was diagnosed at an early stage. All TNBCs present ductal histotype, mostly with high proliferation rate and grading 3. Characteristics of tumors are shown in Table 1. In our cohort, PALB2 mutations were the most frequent PVs in non-BRCA genes, in line with several previous studies. Interesting, we identified RAD51C/D mutations as second PVs non-BRCA genes, in support of certain studies that suggest an association with an increased risk for TNBC and OC. In conclusion, our results support the MGP using, opening the question about the 60-year cut off for genetic testing in TNBC, regardless of family history. Table 1.Characteristics of TNBC tumors in patients carrying other than BRCA gene mutationsPALB2RAD51C/DATMMUTYHBRIPPMS2PTENNBNBARD1CHECK2TP53Number of patients165332111111Mean age at diagnosis (y)61.4 (44-94)48 (33-62)52.3 (49-54)44.3(40-50)42.5 (36-49)394958485036Ki 67 (%)=406(54.5%)4(100%)1(50%)1 (50%)1(100%)100100unknown51111000011GradingG1-23 (25%)0000001000G39 (75%)4 (100%)3 (100%)3(100%)2(100%)110101Unknown41000000010Histotypeductal14 (100%)4(100%)3(100%)3(100%)2(100%)110111others00000001000unknown21000000000Stage at diagnosisI7 (63.6%)3 (60%)01 (100%)1 (100%)010000II4 (36.4%)1 (20%)2 (100%)00001000III01 (20%)000300000unknown50121000111 Citation Format: Laura Cortesi, Marta Venturelli, Angela Toss, Claudia Piombino, Elena Barbieri, Elisabetta Razzaboni, Luca Moscetti, Federico Piacentini, Claudia Omarini, Federica Domati, Massimo Dominici. Characteristics of TNBC patients carrying other than BRCA gene mutations [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-14.

Objective: As prostate cancer (PrC) shows a BRCA mutation rate as high as 30%, it becomes crucial to find the optimal selectioncriteria for genetic testing. The primary objective of this study was to evaluate the BRCA mutation rate in families with PrC associatedwith breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcomeamong BRCA1 and BRCA2 carriers. Methods: Following the Modena criteria for the BRCA test, we evaluated the mutation rate in families with breast and/or ovariancancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. Thecharacteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ2) test and Kaplan–Meier methods,respectively. Results: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modenaselection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positivefor BRCA and one for CHEK2 genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis andin the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the BRCA2 gene fellin the prostate cancer cluster region (PCCR) at the 3′ terminal of the 7914 codon. Conclusions: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancerand PrC. A trend toward a worse prognosis has been found in BRCA2 carriers.

The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability &gt, 5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed &le, 60 years, and 109 luminal-like breast cancer (BC) patients diagnosed &le, 35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% &le, 30 years, 31.8% in patients aged 31&ndash, 40, 16.1% for those aged 41&ndash, 50 and 7.9% in 51&ndash, 60s. A total of 40% of patients with estrogen receptors (ER) 1&ndash, 9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0&ndash, 25 years, 9% between 26&ndash, 30 years and 6% between 31&ndash, 35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed &le, 60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining &lt, 10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

Mutation carriers (Mut+) in DNA mismatch repair genes are predisposed to cancer of various organs and to adenomatous polyps; however, they may remain asymptomatic and cancer or polyp-free for several years. We purposed to analyse the clinical follow-up of individuals carrying constitutional mutations in the MLH1, MSH2 or MSH6 genes who were unaffected by benign polyps or malignant tumours at diagnosis.Mut + subjects (n.81) were members of Lynch syndromes in whom mutations were detected between 1993 and 2015; all were asymptomatic at diagnosis. They were informed of the cancer risk and surveillance was suggested. As controls, 113 nongene carriers (Mut-) in the same Lynch families were identified.About one-fourth of the mutation carriers developed polyps, mostly adenomas; polyps were less (12%, p .05) in Mut - subjects, and hyperplastic lesions were the prevalent histology. More polyps were detected in MLH1 vs. MSH2 mutation carriers. In Mut+, 21 malignant tumours developed in 14 carriers vs. 4 tumours in 3 patients among Mut- (p .001). Tumours were mostly of the Lynch spectrum; however, three glioblastomas were developed, together with neoplasms of various organs (duodenum, thyroid, skin, lung and cervix). Mean age of tumour occurrence was 43.0 years in Mut + vs. 53.0 among Mut-.Cancer developed more often in Mut+, with no consistent difference between MLH1 and MSH2 carriers. More polyps (mostly adenomas) were detected in MLH1 carriers. The majority (13 of 21) of malignant tumours occurred in organs for which there is no recommended surveillance, and were lethal in three patients.

Relatively little is known on the genotype-phenotype correlations between SMAD4 gene mutations, juvenile polyposis of the intestine and Hereditary Hemorrhagic Teleangectasia. We describe a family in which the proband (a 46-year old woman) had massive polyposis of the stomach-leading to surgery-with high-grade dysplasia at histology. Molecular analysis was carried out using Next Generation sequencing techniques with Miseq Illumina Platforms and a minimal coverage of 40 reads. In the proband, the analysis showed the presence of a truncating mutation in the SMAD4 gene (c.1213dupC, a variant previously associated with juvenile polyposis and Hereditary Hemorrhagic Teleangectasia). The same mutation was detected in two other members of the family (father and brother of the proband), who showed massive polypoid involvement of the stomach at gastroscopy. By taking the family history, subtle evidence of Hereditary Teleangectasia was found (nasal bleeding and arterovenous malformations) in the three gene carriers. Colonoscopy showed polyp occurrence in all three affected members with SMAD4 mutation, with prevalence of adenomatous lesions in one (father), of hamartomas in the brother, and of a mix of histological types in the proband. The main features of the family can be summarized as follows: (A) In hereditary juvenile polyposis, lesions of different histology can be detected at colonoscopy; (B) In the gene carriers of SMAD4 mutations, lesions of the stomach require careful surveillance and, when necessary, surgical interventions; (C) Signs and symptoms of Hereditary Hemorrhagic Teleangectasia should be suspected (and searched) in individuals with SMAD4 constitutional mutations.

Aims The clinical outcome of patients with locally advanced rectal cancer who undergo neoadjuvant chemoradiotherapy (CRT) is influenced by the tumour response to treatment, which is reflected by tumour regression grade and post-treatment (y) TNM stage. Little is known about the prognostic value of pretreatment histopathological features of the tumour that may be useful to discriminate potential non-responders and to design tailored therapeutic strategies. In this study, we aimed to investigate the prognostic role of poorly differentiated clusters (PDCs) of neoplastic cells in pretreatment biopsies of patients with rectal cancer treated with neoadjuvant CRT. Methods and results Grading based on PDC counting was retrospectively applied to 204 pretreatment endoscopic biopsies of rectal carcinomas from patients treated with neoadjuvant CRT and surgery. Interobserver agreement in the assessment of PDC grade was good. High PDC grade was significantly associated with high yT stage (P = 0.044), yM+ status (P = 0.0004), and unchanged TNM stage or TNM upstaging (P = 0.032). In addition, high PDC grade was a significant and independent prognostic factor for cancer-specific survival. Conclusions PDC grade may be assessed in preoperative biopsies of rectal cancer with good reproducibility. High PDC grade in a pretreatment tumour is significantly associated with a poor response to therapy. Hence, we suggest that PDC grading might be used as a significant predictive and prognostic factor in patients with locally advanced rectal cancer who are treated with neoadjuvant CRT, and to identify high-risk patients who need surgery and adjuvant chemotherapy.

AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery. METHODS Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses. RESULTS cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

Attenuated polyposis could be defined as a variant of familial adenomatous polyposis (FAP) in which synchronous polyps of the large bowel range between 10 and 99. We analysed all cases of attenuated polyposis observed over the last 30 years with the objectives: (A) to classify the disease according to different type and proportion of polyps; (B) To ascertain the contribution of APC and MutYH genes; (C) to discover features which could arise the suspicion of mutations; (D) To obtain indications for management and follow-up. 84 individuals in 82 families were studied. Polyps were classified into four groups as adenoma, hyperplastic, other serrated lesions or others; APC and MutYH mutations were assessed. Mean age at diagnosis was 54 ± 14 years in men and 48 ± 13 in women (P = 0.005). Polyps were more numerous in women (37 ± 26 vs 29 ± 22). Sixty % of patients underwent bowel resection, mainly for cancer; the remaining were managed through endoscopy. A total of 2586 polyps were detected at diagnostic endoscopy: 2026 (80 %) were removed and analysed. Adenomas were diagnosed in 1445 (70 %), hyperplastic polyps in 541 (26 %), other serrated lesions in 61 (2.9 %). Adenomas and hyperplastic lesions were detected in the majority of patients. In 68 patients (81 %) in whom studies were executed, APC mutations were found in 8 and MutYH mutations in 10. Genetic variants were more frequent in women (12 vs 6, P = 0.039). Taking into consideration the prevalent (>50 %) histology and presence of mutations, patients could be subdivided into four groups: (1) APC mutated polyposis (AFAP), when adenomas were >50 % and APC mutations detected (no. 8, 10 %); (2) MutYH mutated polyposis (MAP), adenomas >50 % and biallelic MutYH mutations (no. 10, 12 %); (1) attenuated polyposis without detectable mutations, prevalence of adenomas, 48 cases (57 %); (1) hyperplastic-serrated polyposis, with prevalence (>50 %) of hyperplastic/other serrated lesions and no constitutional mutation (no. 18, 21 %). Aggregation of tumors, cancer in probands, distribution of polyps and other clinical characteristics showed no difference among the four groups. In conclusions, AFAP and MAP, the polyposis labeled by constitutional mutations, represented about 25 % of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex.

Background The counting of poorly differentiated clusters of 5 or more cancer cells lacking a gland-like structure in a tumor mass has recently been identified among the histological features predictive of poor prognosis in colorectal cancer. Main body Poorly differentiated clusters can easily be recognized in the histological sections of colorectal cancer routinely stained with haematoxylin and eosin. Despite some limitations related to specimen fragmentation, counting can also be assessed in endoscopic biopsies. Based on the number of poorly differentiated clusters that appear under a microscopic field of a ×20 objective lens (i.e., a microscopic field with a major axis of 1 mm), colorectal cancer can be graded into malignancies as follows: tumors with

Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15–20 % of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena—(Northern Italy) within the 2002–2006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7 % (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p

To assess whether any relationship exists between the number of histologically examined lymph nodes and the detection of metastases in pelvic lymph node dissection (PLND) specimens taken from patients with radical prostatectomy (RP) for prostatic adenocarcinoma. 1690 cases of RP with PNLD were included in the study; 54 % of the patients were submitted to extended PLND (ePLND). Kaplan-Meier curves confirm the negative prognostic significance of nodal metastases on the overall patients' survival (P < 0.0001). Nodal metastases are significantly associated with older age of patients (P = 0.0466), higher pT status (P < 0.0001), higher Gleason score (P < 0.0001) and positive surgical margin (P < 0.0001). The frequency of nodal metastases is significantly increased in cases submitted to ePLND (P < 0.0001), presumably due to the significantly higher number of lymphnodes retrieved using this procedure (P < 0.0001). In addition, regardless of the extent of PLND procedure, entire histological examination of PLND specimens is significantly associated with a higher frequency of nodal metastases (P < 0.0001). When we considered only pN0 cases, 21 display adverse prognosis and died of disease during the follow-up. The number of pelvic lymphnodes examined is significantly lower in the group of patients who die of the disease compared to that of survivors (P = 0.0448). In addition, Kaplan-Meier analysis shows that patients with 10 or fewer examined lymphnodes have significantly shorter disease-specific survival (P = 0.0151). Our findings confirm the negative prognostic significance of N status in prostate cancer. We suggest the examination of a minimum number of 10 lymphnodes, together with entire PLND processing, for accurate assessment of N status.

Signet ring cell carcinoma (SRCC) is a rare variant of colorectal cancer (CRC), by definition composed of at least 50 % of neoplastic cells showing signet ring cell morphology. Colorectal SRCC is mainly characterized by aggressive clinical behavior, high pTNM stage and microsatellite instability (MSI). We assessed the prognostic value of several histopathological parameters (histological grade, venous invasion, lymphovascular invasion, MSI, mucin content, tumour budding, pTNM stage) in terms of disease free survival (DFS) and cancer specific survival (CSS) in a series of 32 SRCCs. We confirm that pTNM stage at diagnosis is relevant for predicting DFS and CSS in SRCC. In addition, we show on haematoxylin and eosin or immunohistochemically stained (CD34, podoplanin) sections that venous invasion and lymphovascular invasion are significantly associated with shorter DFS and CSS in SRCC. Notably, venous invasion assed by immunohistochemistry had the highest risk ratio and proved to be the only independent prognostic variable. Finally, we show that histological grade, as assessed on the percentage of formed glands, has prognostic relevance in SRCC as high-grade tumours (

There is a need for more information on the quality of life (QoL) in patients undergoing chemotherapy. We wanted to investigate the perception of health status in colon cancer patients before, 3 and 6 months after chemotherapy. A secondary purpose was to assess the different perceptions of QoL between men and women during and after adjuvant or palliative therapy. We investigated 100 patients throughout chemotherapy for colon cancer. Data were collected through the SF-36 questionnaire. The score of all variables analyzed in the study group was lower than in the control group, which indicates a lower performance status, more marked in the female sex. Patients were then subdivided by the state of disease (localized or metastatic) and the variables, were evaluated before, 3 and 6 months after therapy. In patients treated with adjuvant treatment, there was a worsening of the performance status, followed by an increase after 6 months. We found that after 3 months of therapy, affected male patients perceived more limitations in carrying out their work, other daily activities and social relationships, owing to both their emotional state and their physical health. In metastatic patients the values of the eight variables decreased dramatically after 6 months, indicating a worsening of the QoL. In patients who received adjuvant treatment there was a certain worsening of the health status at 3 months, followed by a general improvement after 6 months. This improvement was not observed in patients undergoing palliative therapy. Several differences were observed between men and women in performance status after treatment.

Objective. In order to identify the radiotherapy-induced histological modifications in the mesorectum, we reviewed the surgical specimens of 90 rectal resections comprehensive of the total mesorectal excision (23 cases radiologically classified as cT2N0M0 and 67 as cT3N0M0). All patients were preoperative treated with radiotherapy: 20 with 50 Gy, 20 with 20 Gy and 50 Gy irradiation associated to FOLFOX scheme chemotherapy. Material and methods. Routine hematoxylin and eosin stained serial slides at 5 mm of intervals were obtained from surgical specimens and included the tumor site and the adjacent irradiated mucosa, the submucosa and the muscular layers of the rectal wall and the mesorectal adipose tissue, completely removed until to the mesorectal fascia. Ten subjects (eight cT2N0M0 and two cT3N0M0), who did not received preoperative oncological treatments were adopted as controls. Results. Histologically, examination revealed fibrosis of the adipose tissue in 86 cases (95%), vascular damage including vasculities and fibrotic thickening wall of arteries and veins in 46 cases (51%), sclero-hyalinosis of lymph nodes with pericapsular fibrosis in 22 cases (23%) and perineural deposition of fibrosis in 12 (13%). These findings were ubiquitously observed in the whole mesorectum. Fibrosis of the adipose tissue and vasculitis were mainly associated to the combination of 50 Gy radiations plus chemotherapy (p < 0.05). Conclusion. The detection of histopathological alterations in the mesorectum can give reason of the well-known postoperative complications and long-term sequels.

Mucinous adenocarcinoma (MAC) of the colon and rectum is a histological entity with still indefinite prognostic significance. Although it was previously designated as poorly differentiated by convention, the most recent World Health Organization guidelines indicate that the level of maturation of the epithelium determines differentiation in MAC and that microsatellite instability status should be taken into account for its histological grading. Nonetheless, precise criteria for grading are not provided, and the prognostic value of histological grading in MAC still remains unclear. In the present study we aimed to investigate the prognostic value of a grading system based on the counting of poorly differentiated clusters (PDC) of neoplastic cells in 108 colorectal MACs and to compare its reproducibility and significance with those of a grading system based on glandular differentiation. We found that PDC grade was more reproducible and significantly associated with disease progression (P = .0089) as well as with death from colorectal cancer (P = .0035) in our MACs, as compared to the grade based on glandular differentiation, which was not associated with any of the clinicopathologic variables. Moreover, PDC grade emerged as a significant, independent prognostic factor of recurrence-free survival (P = .0198) and cancer-specific survival (P = .0293) in MAC. Interestingly, the prognostic value of PDC grade was unaltered following incorporation of mismatch repair system status in grading. In conclusion, we demonstrated for the first time that PDC grading is feasible, reproducible, and prognostically relevant in MAC, which may support its use in routine practice.

We report the clinical case of a patient who showed an “accelerated” form of polyposis, with development of major lesions within the first decade of life. The patient belongs to a familial adenomatous polyposis family—already described in 2001—featured by profuse polyposis at an early age of onset and desmoid tumors in the majority of affected individuals (of both sexes). The family was characterized by an uncommon mutation of the APC gene (c.4391_4700del310insCACCTACTGCTGAAA, previously defined as c.4394ins15del310) consisting in a large deletion of 310 bp at codon 1,464 with duplication of the breakpoint leading to a stop codon at position 1,575. The proband was affected by desmoids tumors at the age of 3 years. In the same year (2004) numerous polyps in the large bowel and a hepatoblastoma developed. After several months new desmoids appeared in the surgical scar. In 2010, at age 9, the patient was operated of total colectomy and endorectal pull-through of the small intestine owing to profuse colorectal adenomatosis. New desmoids developed in 2011 and 2012, and required chemotherapy. Further analysis of the APC gene in the proband revealed several polymorphisms. One of these (c.398A>G) had not been previously reported, nor was present in two other affected members of the family. The clinical case, and the practical implications for therapy, are discussed according to the most recent theories of colorectal cancer development. Long-term treatment with Cox-2 inhibitors might represent a good option for this patient.

The aim of the study was to investigate the clinical features, including survival, of patients with colorectal malignancies developed at a very early age (≤40 years), together with possible factors involved in the pathogenesis of these rare neoplasms. The study took advantage of the existence of a specialized colorectal cancer Registry active from 1984. 57 patients met the criteria of early onset cancer; main epidemiological data, morphology, stage, familial aggregation, possible role of inheritance and survival were analyzed. Despite the relevant increase over time of all registered patients, joiningpoint analysis of crude incidence rate of early onset colorectal neoplasms revealed a certain stability of these tumors (EAPC: 2.4, CI 14–22) with a constant prevalence of the male sex. Stage at diagnosis did not show significant variations between early onset and maturity onset colorectal neoplasms. Hereditary as well as familial cases were significantly (P < 0.005 and 0.03) more frequent among patients with early onset tumors, although in the majority of them no specific etiological factor could be identified. Survival was more favorable in patients with early onset tumors, though this had to be attributed to the higher presence of some histological types in early onset cases. Survival was significantly more favorable for patients of all ages registered in the last decade. Incidence of early onset colorectal cancer was relatively stable between 1984 and 2008. A male preponderance was evident through the registration period. Hereditary and familial cases were significantly more frequent among early onset case. A well defined etiology could be observed in 16 % of the cases (versus 2–3 % in older individuals). Five-year survival showed a significant improvement over time.

The purposes of the study are to describe the incidence trend of malignant polyp of large bowel over a 25-year period in the District of Modena and to assess the effect of an organized colorectal cancer screening program.Through the data of a specialized colorectal cancer Registry, we evaluate the clinical and pathological features of the polyps. Trend analysis was assessed with the Joinpoint Regression Program.A total of 172 patients with malignant polyps were diagnosed throughout the study (3.5% of 4.835 registered patients); their overall frequency during the registration period increased from zero cases in the initial years (1984-85) to 57 cases in the past 3 years (2006-2008). Crude incidence rate passed from 0.37 in 1986-89 to 10.2 in 2006. Joinpoint trend analysis of crude rates showed a significant increase of incidence during the study period, with percent of annual variation ranging between 38.6% (95% CI 12.5-70.7) and 7.3% (95% CI 2.6-12.1). During the screening period (2005-2008, the past 4 years of registration) there was a significant increase of sessile polyps (p0.001), while other clinical and morphological features, including the number of low- and high-risk malignant polyps, remained unchanged. The surgery (after polypectomy) tended to raise both in low- and high-risk subgroups.The incidence of malignant polyps increased significantly from the initial to the most recent periods of colorectal cancer registration. Screening was associated with changes in gross morphology of polyps and with an increased use of the surgery after endoscopic polypectomy.

Colorectal cancer can be a painful event, generally associated with changes in lifestyle for many patients. We studied the quality of life of the patients operated for colorectal malignancies 5 years after the diagnosis. Using detailed questionnaires, we investigated 220 patients of both sexes (mean age 66.5 years) 5 years (or more) after a curative operation for cancer of the large bowel. The short form 36 (SF-36) questionnaire took into consideration several aspects concerning work activity, physical activity, psychological attitude, alimentation, familial relationships, and other relevant components of lifestyle. Moreover, we compared the perception of the so-called SF-36 score between our patients and a comparison group in the general population. Both univariate and multivariate analysis were used. The obtained results revealed that familial and social relations were equally unchanged or tended to improve. Sexual activity declined in only 61(31.3%) subjects. Rather surprisingly (because of the average age at diagnosis), work activity remained unchanged in about half of the patients. Using the SF-36 questionnaire, the main differences from the general Italian population were seen in bodily pain (especially in the few individuals in whom a permanent stoma was necessary), social functioning and general physical health. In conclusion the results seem to suggest that the majority of patients who survive for more than 5 years after an operation for colorectal malignancy return to an almost normal life. The awareness among individuals about their disease, the improvements in surgical techniques and medical treatments are among the factors responsible for these positive results.

Screening and early diagnosis of cancer represent relatively recent tools in the long-lasting battle against tumors. If the American public opinion manifests its enthusiasm towards screening, the attitude of European is less well known. The purpose of the present study was to assess the level of knowledge and awareness of cancer screening (with particular emphasis on colorectal neoplasms) among middle-aged individuals. The study group consisted of 945 healthy individuals (489 men, 456 women, average age 57 +/- 12.4 years) who were asked to answer a series of questions about cancer screening and surveillance through a questionnaire presented by trained residents. Each interview lasted 20-30 min. Middle-aged Italians of both sexes seem to be aware of the fact that cancer is a frequent disease; moreover, many of the interviewed subjects believe almost all neoplasms are incurable. Diet, style of life, other environmental factors and familial factors are fully appreciated as relevant risk factors. The exact meaning of prevention was clear to less than half of the subjects. When various cancer sites were analyzed, the existence of preventive measures was well known for breast, cervical and prostate tumors, but their role was less clear for colorectal cancer. Only a fraction of the interviewed individuals were willing to undergo screening; the main reasons for refusal were lack of usefulness and fear of results. Among various tests, ultrasound and endoscopy were usually carried out in the presence of symptoms. Finally, multivariate analysis showed that the two factors significantly associated with the decision to undergo screening procedures were increasing age and level of education. The results of the study suggest that middle-aged Italian individuals, predominantly from Northern regions, have a correct perception of some aspects (frequency, risk factors) of cancer biology, whereas the knowledge of other aspects (outcome, prevention) remains poor or approximate. It follows that one of the main objectives of the Political Class should be to obtain a better education of overage individuals about cancer and the many problems related to this common disease.

e13674 Background: BRCA germline (gBRCA) mutations occur in 11-15% of women with unselected ovarian cancers (OC), whereas somatic BRCA (sBRCA) mutations occur in approximately 5-7% of cases. The impact of sBRCA mutations on OC outcome is still debated. Methods: With the aim to explore the prognostic role of sBRCA mutations, the BRCA mutational status of 149 non-mucinous and non-borderline OC and their clinical-pathological features were evaluated. BRCA1 and BRCA2 mutational profiles, either for sequence variants or copy number alterations, were evaluated by amplicon next-generation sequencing (NGS) technology. Results: 29 (19.5%) patients carried a gBRCA mutation (12.7% BRCA1 and 6.7% BRCA2). 26 (17.5%) patients presented a sBRCA mutation (6.7% BRCA1, 10% BRCA2, 0.6% BRCA1+BRCA2). Patients carrying a gBRCA mutation were slightly younger (57 years) than the others (60 years). The FIGO stage at the diagnosis was III-IV in 77.2% of cases, with no significant difference among subgroups. The most frequent histotype was serous for all the subgroups (93.1% in gBRCA, 84.6% in sBRCA, 77.7% in BRCA-negative, p = 0.08). 80.7% of sBRCA mutation carriers, 62.1% of gBRCA mutation carriers and 62.7% of BRCA-negative patients underwent upfront surgery (p = 0.46). 29.1% of sBRCA mutation carriers, 17.8% of gBRCA mutation carriers and 25.6% of BRCA-negative patients presented macroscopic residual disease after surgery (p = 0.68). Although non-statistically significant, gBRCA-associated OC were more likely to be platinum-sensitive (96.6%) than the other patients (92% in sBRCA and 87.1% in BRCA-negative patients). Overall, the median platinum-free interval (PFI) resulted shorter in sBRCA mutation patients compared to gBRCA and BRCA-negative patients (p = 0.051). No patient took PARP inhibitors as maintenance after the first line therapy. Also progression free survival 2 (PFS2) resulted shorter for sBRCA mutation patients (p = 0.008). Three sBRCA and 5 gBRCA mutation carriers took a PARP inhibitor as maintenance after the second line therapy. Finally, sBRCA mutated patients showed worse overall survival (OS) compared to the other subgroups (p = 0.014). Conclusions: Overall, 19.5% of OC patients presented a gBRCA mutation, while 17.5% of patients showed sBRCA mutations. sBRCA-related OC did not show significantly differences in clinical-pathological features (stage at diagnosis, histotype, time to surgery and residual after surgery). To our knowledge this is the first study showing shorter PFI, PFS2 and OS in patients carrying sBRCA mutations.