Colorectal cancer in young adults: a retrospective study of 32 tunisian patients.

Young people under the age of 40 with colorectal cancer represent a distinct subgroup with a more aggressive disease behaviour compared to older patients. This study aim to provide an updated overview on clinicopathological features, treatment and outcome of colorectal cancer in young adults under the age of 40. In our retrospective study, we reviewed 32 cases of colorectal cancer in young adults aged less than 40 years that were diagnosed at the pathology department of Mongi Slim hospital over a fifteen-year period (April 2000 - November 2014). Our study group included 13 male and 19 female patients (sex-ratio M/F = 0,68) between 17 and 39 years of age (mean = 31,25 years). The presenting clinical symptoms were dominated by altered bowel habits (n=17), followed by bleeding per rectum (n=16). Histopathological examination of the surgical and biopsy specimens established the diagnosis of mucinous adenocarcinoma in nine cases, well-differentiated adenocarcinoma in 11 cases, moderately differentiated adenocarcinoma in six cases, poorly differentiated adenocarcinoma in four cases and signet ring cell carcinoma in two cases. The tumours were classified after surgery as stage I (n = 2) (6%), stage IIA (n = 7) (22%), stage IIB (n=4) (13%), stage IIC (n=1) (3%), stage IIIB (n=8) (25%), stage IIIC (n= 4) (12%), stage IVA (n=4) (13%) and stage IVB (n=2) (6%). During the follow-up period which ranged between one month and 9 years, local recurrence of the tumour occurred in six cases, seven patients had hepatic metastases and seven patients died after a mean follow-up period of seven months. Molecular genetic studies are increasing the understanding of the pathobiology of colorectal cancer and may ultimately allow at-risk patients to be identified at an earlier stage.

Solid pseudopapillary neoplasm of the pancreas in two male patients: gender does not matter.

Solid pseudopapillary tumour (SPT) is an unusual pancreatic neoplasm which predominantly affects young women. Less than 10% of patients with SPT in the reported literature were male. In this paper, the authors report two new cases of SPT that occurred in two male patients aged respectively 25 and 20 years old. Abdominal computed tomography scan showed a well-defined heterogeneous mass involving respectively the tail and the body of the pancreas with peripheral calcifications in the first case. The two patients underwent distal splenopancreatectomy. Histopathological examination of the surgical specimen coupled with immunohistochemical study was compatible with solid pseudopapillary tumour. On postoperative day 8, the first patient developed abdominal wall abscess and peritoneal collection. Postoperative course was uneventful for the second patient. In summary, a large, well-encapsulated cystic mass in the pancreas of a young man should raise suspicion of solid pseudopapillary tumour.

Hepatocellular carcinoma: a clinicopathological study of 64 cases.

Hepatocellular carcinoma (HCC) is the most common of all liver cancers and is a major worldwide public health problem. The aim of this study was to provide an updated overview on clinicopathological features, treatment and outcome of HCC. In our retrospective study, we reviewed 64 cases of HCC that were diagnosed at the pathology department of Mongi Slim hospital over a fifteen-year period (2000- 2014). Relevant clinical information and microscopic slides were retrospectively reviewed. Our study group included 38 men and 26 women (sex ratio M/F = 1,26) aged between 8 and 83 years (mean = 56,64 years). The presenting clinical symptoms were dominated by abdominal pain (n=34), followed by altered general health (n=25) and jaundice (n=4). Fifty-five patients underwent surgical treatment. Liver transplantation was performed in two cases and transarterial chemoembolization was achieved in seven cases. Histopathological examination of the surgical or biopsy specimen established the diagnosis of conventional HCC in 55 cases, fibrolamellar carcinoma in 6 cases and clear cell HCC in 3 cases. Seven patients with HCC died postoperatively. Local recurrence of the tumour occurred in three cases and two patients had distant metastases postoperatively. The other patients are still being followed-up. Hepatocellular carcinoma is associated with a high rate of mortality because of early invasion, widespread metastasis and lack of effective therapeutic modalities. Accurate diagnosis and staging of these tumours is critical for optimal treatment planning and for determining prognosis.

Routine histopathological study of cholecystectomy specimens. Useful? A retrospective study of 1960 cases.

BACKGROUND AND AIMS: Traditionally, a gallbladder removed for presumed benign disease is sent for histopathological examination, but this practice has been the subject of controversy. AIM: The aim of this study was to assess the usefulness of routine histopathological examination of cholecystectomy specimens and its impact on the management of patients. PATIENTS AND METHODS: The histopathological reports of 1960 patients who underwent cholecystectomy from January 2011 to November 2016 were retrospectively reviewed. Results : There were 519 men and 1441 women (sex-ratio M/F = 0,36) aged between 8 and 96 years (mean = 51,23 years). All patients underwent cholecystectomy (either open or laparoscopic). Histological examination of the surgical specimens showed chronic cholecystitis (n = 1319) (67,29%), acute cholecystitis (n = 117) (5,96%), cholestrolosis (n = 255) (13%), follicular cholecystitis (n = 230) (11,73%), xanthogranulomatous cholecystitis (n = 6) (0,30%), cholesterol polyps (n = 5) (0,255), tubular adenoma (n = 3) (0,15%), mucocele (n = 2) (0,10%), pancreatic heterotopia (n = 2 ) (0,10%), hyperplastic Luschka ducts (n = 2) (0,10%), adenomyoma (n = 2) (0,10%), porcelain calcification (n = 2) (0,10%) and biliary-type adenocarcinoma (n = 9) (0,46%). In 9 cases (0,46%), the gallbladder was histologically normal. CONCLUSION: Our study shows that the incidence of pre-malignant and malignant lesions of the gallbladder is very low. We therefore recommend selective histopathological examination of cholecystectomy specimens with abnormal macroscopic findings.

Crohn's disease and schistosomiasis: a rare association.

Schistosomiasis is a chronic enteropathogenic disease caused by blood flukes of the genus Schistosoma. Coexistence of schistosomiasis with Crohn's disease is very rare. To the best of our knowledge, this association has been described in literature only once. A 20-year-old male patient with a past medical history of appendectomy and ileocecal Crohn's disease, presented with abdominal pain and vomiting. Ileocolonoscopy showed an ulcerated and congested appearance of the upper rectum and sigmoid. Computed tomography scan revealed a circumferential thickening of the terminal ileum with luminal stenosis. Histopathological examination of the biopsy specimens revealed a focally ulcerated colonic epithelium. The lamina propria was fibrous harbouring a polymorphic inflammatory infiltrate including lymphocytes and plasma cells organized in lymphoid follicles admixed with eosinophils and neutrophils. In the submucosa, there were two well-preserved schistosoma eggs surrounded by a thick shell with a barely visible terminal spine. The final pathological diagnosis was colonic schistosomiasis associated with Crohn's disease. The patient underwent an ileocecal resection for stenosis of the terminal ileum complicated with enterocutaneous fistula. The postoperative course was uneventful. A stool examination and serology tests were planned for this patient who was lost to follow-up.

Fibrolamellar carcinoma versus scirrhous hepatocellular carcinoma : diagnostic usefulness of CD68.

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma that commonly affects young individuals without a prior history of liver disease. The principal differential diagnosis is conventional hepatocellular carcinoma especially the scirrhous variant. Despite their distinctive appearance, recent studies have demonstrated a lack of consistency in how FL-HCC are diagnosed by pathologists. AIM: To investigate the diagnostic utility of CD68 in differentiating between FL-HCC and scirrhous hepatocellular carcinoma. PATIENTS AND METHODS: In our retrospective study, we reviewed four cases of FL-HCC that were diagnosed at the pathology department of Mongi Slim hospital over a thirteen-year period (2002-2014). Relevant clinical information and microscopic slides were available in all cases and were retrospectively reviewed. Immunohistochemical analysis was performed using the avidin-biotin complex technique with antibodies against CD68 and CK7. RESULTS: Our study group included one man and three women (sex ratio M/F=0.33) aged between 23 and 34 years (mean=28 years). All cases arose in non-cirrhotic liver. Immunohistochemically, all cases were positive for CK7 and for CD68 (n=4). CONCLUSIONS: CD68 immunostaining is a sensitive marker for FL-HCC that may be of use in routine diagnostic surgical pathology. Lack of CD68 staining should suggest caution in making a diagnosis of FL-HCC.

Unexpected Histopathological Findings in Appendectomy Specimens: a Retrospective Study of 1627 Cases.

Pathologic evaluation of the appendix after appendectomy is routine and can occasionally identify unexpected findings. The aim of the present study was to determine the incidence and type of pathologic diagnoses found in appendectomy specimens at our institution. The clinicopathological data of 1627 patients who underwent appendectomies for presumed acute appendicitis from January 2008 to October 2014 were reviewed retrospectively. There were 986 men and 641 women (sex ratio M/F = 1.5) aged between 16 months and 90 years (mean = 30 years). All patients underwent appendectomy (either open or laparoscopic). Histological examination of the surgical specimen showed acute inflammation of the appendix in 1455 cases (89.42 %), fibrosed appendix in 37 cases (2.27 %), and Enterobius vermicularis (n = 23). In 101 cases (6.2 %), the appendix was histologically normal. Incidental unexpected pathological diagnoses were noted in 57 appendectomy specimens. They included pinworm (n = 23), mucinous neoplasms (n = 12), neuroendocrine tumors (NET) (n = 8), adenocarcinoma (n = 2), granulomatous inflammation (n = 5), tuberculosis (n = 2), hyperplastic polyp (n = 1), tubular adenoma (n = 1), diverticulitis (n = 1), endometriosis (n = 1), and actinomycosis (n = 1). The routine histopathological examination of the appendix is of value for identifying unsuspected conditions requiring further postoperative management. Gross examination alone does not appear to be a good indicator of an unexpected finding on microscopic exam. It is recommended that in order to avoid misdiagnoses, all appendices should be histopathologically examined.

Relationship between SDF-1G801A polymorphism and its expression in Tunisian patients with colorectal cancer.

The aim was to evaluate the relationship between SDF-1G801A polymorphism and its immunohistochemical expression in colorectal cancer tissues in the Tunisian cohort. The molecular and immunohistochemical analysis showed that SDF-1G801A polymorphic variant was higher in CRC patients with TNM stage II and III, the SDF-1 expression was significantly increased from normal mucosa to primary tumor (p < 0.05). CRC patients have higher frequency of A allele (52.01%) than controls (26.8%) (P = 0.0001). Thus, SDF-1 polymorphism is a risk factor of colorectal cancer susceptibility in our population, the polymorph genotype of SDF-1 maybe associated with clinical manifestations in CRC patients in Tunisia.

Primary hepatic vascular tumours. A clinicopathologic study of 10 cases.

BACKGROUND: Primary hepatic vascular neoplasms constitute a heterogeneous group of neoplasms with characteristic histology and variable tumour biology. AIM: To provide an updated overview on clinicopathological features, treatment and outcome of primary hepatic vascular tumours. PATIENTS AND METHODS: In our retrospective study, we reviewed 10 cases of primary hepatic vascular tumours that were diagnosed at the pathology department of Mongi Slim hospital over a thirteen-year period (2000-2012). Relevant clinical information and microscopic slides were available in all cases and were retrospec- tively reviewed. RESULTS: Our study group included 4 men and 6 women (sex ra- tio M/F = 0.66) aged between 23 and 78 years (mean = 55.5 years). Based on imaging studies, preoperative diagnosis of hemangioma was accurately made in only three cases. Three cases were misdiagnosed preoperatively as having hydatid cyst and four cases of hemangiomas were misdiagnosed preoperatively as liver metastases. All our patients underwent surgical resection of the tumour. Histopathological examination of the surgical specimen established the diagnosis of angiosarcoma in one case, cavernous hemangioma in 8 cases and sclerosing hemangioma in one case. CONCLUSION: Hepatic tumours are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumours is of major importance for clinical practice. Definitive diagnosis is based on histopathologic examination.

Pancreatic cystic neoplasms.

BACKGROUND: Cystic neoplasms of the pancreas are rare and constitute approximately 0.5% of all pancreatic neoplasms. AIMS: The study was to describe clinicopathological features of pancreatic cystic tumors. PATIENTS AND METHODS: In our retrospective study, we reviewed 10 cases of pancreatic cystic neoplasms that were diagnosed at the pathology department of Mongi Slim hospital over a 14-year period (2000-2013). We adopted the latest World Health Organization (WHO) classification (2010) in grouping all tumors. RESULTS: There were one male and nine female patients (sex ratio M/F = 1:9) aged between 21 and 68 years (mean = 37.5 years). The most common clinical presentation was epigastric and abdominal pain (n = 6) followed by vomiting (n = 3). Abdominal computed tomography (CT) scan disclosed a cystic lesion of the pancreas ranging in size between 2 and 10 cm (mean = 6.75 cm). All patients underwent surgical treatment. Histopathological examination of the surgical specimen established the diagnosis of solid pseudopapillary neoplasm (n = 2), serous cystic neoplasm (n = 2), mucinous cystadenoma (n = 4), mucinous cystadenocarcinoma (n = 1), and intraductal papillary mucinous neoplasm with invasive carcinoma (n = 1). CONCLUSION: Better understanding of pancreatic cystic neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.

Co-existence of hepatocellular carcinoma and hepatic tuberculosis.

BACKGROUND: Many case reports describe tuberculosis (TB) co-existent with a malignant neoplasm. However, the neoplasm in most of these reports is lung or breast cancer, with only two cases of liver cancer concomitant with TB reported in the literature. Although both TB and cancer are very common diseases, little attention has been given to the pathophysiologic and practical implications of their co-existence. METHODS: Case report and literature review. CASE REPORT: A 73-year-old female patient with a history of hypertension and hepatitis C presented with abdominal pain of 2 mos duration. Laboratory findings showed an elevated serum concentration of α-fetoprotein. A computed tomography scan demonstrated a solitary hypodense tumor in the right lobe of the liver (segment VIII). A pre-operative chest radiograph was within normal limits. The patient underwent an uneventful tumor resection. Histologic examination of a surgical specimen of the tumor demonstrated a moderately differentiated hepatocellular carcinoma co-existent with caseating granulomas. CONCLUSION: Through this case report, the authors discuss the pathogenesis of the rare association of TB and malignant neoplasm of the liver, and present a review of the current literature on the association of TB and cancer. Further research is required to determine whether a TB infection resembles other chronic infections and inflammatory conditions in having a potential to facilitate oncogenesis.

Biological significance of promoter hypermethylation of p14/ARF gene: relationships to p53 mutational status in Tunisian population with colorectal carcinoma.

One of the most important pathways which are frequently affected in colorectal cancer is p53/ (MDM2)/p14ARF pathway. We aim to determine the methylation pattern of p14/ARF in relation to mutation of p53. This correlation was studied to investigate whether their alterations could be considered as a predictor factor of prognosis in colorectal cancer and whether it can be useful in early-stage diagnosis. Statistical analyses show that p14/ARF hypermethylation was correlated with rectum location (p = 0.004), primary TNM stage (p = 0.016), and advanced Astler-Coller stage (p = 0.024). The RT-PCR that revel 31 % of patients did not express p14/ARF mRNA or at very low level. A high concordance between CpG hypermethylation and the low levels (p < 0.005) was shown. In addition, our analyses demonstrate that patients with mutation in the p53 gene have a lack of the protein expression (p < 0.005). This category with negative expression of p53 had a shorter survival rate (p < 0.005). On the one hand, MSP pattern of p14/ARF were correlated with a lack of p53 expression (p = 0.007). We found that p53/p14ARF pathway was frequently deregulated among our patients. In our study, we demonstrate that hypermethylation of p14/ARF occurs early during CRC tumorogenesis. However, we did not find correlation between p14/ARF and survival. These results suggest that p14/ARF methylation pattern may constitute a predictor factor of CRC in early stage but it could not be considered as a prognostic factor. On the other hand and because of the reversibility of the methylation mechanism, it may be appropriate to target the demethylation of p14/ARF to develop new drogues for CRC.

Relationship between MDM2 and p53 alterations in colorectal cancer and their involvement and prognostic value in the Tunisian population.

BACKGROUND: The prevalence of p53 mutations in colorectal cancer could reach 90%. The most important regulator of this protein that was identified originally was the Murine Double Minute2 (MDM2) oncoprotein, by which the levels of p53 were fixed through an autoregulatory feedback loop. In cancer cases, the overexpression of MDM2 deregulates this feedback, and the signaling pathway between MDM2 and p53 is blocked. MATERIALS AND METHODS: We genotyped 167 patients and 167 healthy blood donors to determinate the mutational status of MDM2 and p53. Immunohistochemical analysis was performed on tumor and normal mucosa. RESULTS: The MDM2 polymorphism study showed a higher distribution of MDM2 SNP309 in tumors compared with healthy controls. At the same time, the majority of samples with SNP309 indicated a positive expression of MDM2 protein in the tumor. In this case, we found a first significant association between p53 expression and the single-strand conformational polymorphism analysis and a second association between the MDM2 polymorphism and p53 mutation. Moreover, the nuclear overexpression of MDM2 and SNP309 was significantly related to a higher mortality rate. CONCLUSIONS: In this work we wanted to highlight the role, which is becoming increasingly important, of MDM2. In fact, we conclude that the effects of MDM2 SNP309 may be considered a valuable prognostic marker to predict poor outcome for Tunisian patients with colorectal cancer.

Evaluation of microsatellite instability, MLH1 expression and hMLH1 promoter hypermethylation in colorectal carcinomas among Tunisians patients.

BACKGROUND: About 10% to 15% of sporadic colorectal cancers demonstrate high level of microsatellite instability that is generally associated with aberrant methylation of hMLH1 promoter. AIM: To investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter in a cohort of Tunisian sporadic colorectal cancer. METHODS: Expression of MLH1 and MSH2 was determined by immunohistochemistry and the MSI status was analysed by microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter was determined by methylation-specific PCR. RESULTS: Of the 150 colorectal cancers 57% were MSS, 28% were MSI-L and 15%were MSI-H. MSI-H tumors were more frequently right-sided, exhibited a stage III of TNM and tended more to be mucinous. The MSI status had no effect on overall patient survival. Most of the MSS/MSI-L 79% cancers were unmethylated at the hMLH1 promoter, while 26% MSI-H cancers were unmethylated. 84% of MSS and MSI-L expressed MLH1 and 52% of MSI-H expressed MLH1. Of the methylated MSI-H cases, 35% expressed MLH1 protein while 100% of the unmethylated MSI-H were positive for MLH1 staining. Of 11 MSI-H cancers with loss of MLH1 expression, all cases were also methylated while 50% MSI-H cancers with positive immunostaining for MLH1 were methylated at the hMLH1 promoter. CONCLUSION: Our study showed that MSI-H phenotype was mucinous, right-side and exhibit stade III of TNM. The relative correlation of MLH1 expression and promotor hypermethylation of hMLH1 for the MSI status is similar to that reported for several study.

Impact of MDM2 polymorphism: increased risk of developing colorectal cancer and a poor prognosis in the Tunisian population.

INTRODUCTION: MDM2 was originally identified as an oncoprotein that binds to p53 and inhibits p53-mediated transactivation. Scientists have described functional single-nucleotide polymorphisms (SNP) in the MDM2 gene. They showed that the genotype of SNP 309 induces an increase in the level of MDM2 protein, which causes attenuation of the p53 pathway. In this study, we sought to investigate whether this polymorphism was related to risk of colorectal cancer and whether there were relationships between SNP 309 and protein expression or clinicopathological variables in Tunisian patients. MATERIALS AND METHODS: To investigate the effect of this polymorphism in colorectal cancer pathogenesis, we genotyped 167 patients and 167 blood donors. Immunohistochemistry was performed on normal mucosa and tumor. RESULTS: The rates of MDM2 genotypes were 6.6% for wild-type (T/T) and 93.4% for the SNP 309 polymorphic genotype (T/G and G/G) in patients and 38.3 and 61.7% in controls, respectively. There were significant differences in the frequencies of genotypes between patients and controls (P<0.01). We did not find any relationship between genotypes and clinicopathological features of patients, except in the case of the nonmucinous histological subtype (P=0.001). Moreover, we found that patients with the wild-type genotype (T/T) had significantly more favorable clinical outcome than did patients with the SNP 309 genotype (T/G, G/G) (P=0.005). In addition, we found an association between positive expression of p53 and polymorphic genotypes of MDM2 (T/G, G/G) (P=0.037). There was a significant association between tumoral immunostaning and MDM2 polymorphism (P=0.01). CONCLUSION: Our results suggest that the MDM2 polymorphism is significantly associated with colorectal cancer risk and may provide useful prognostic information for Tunisian patients with colorectal cancer.

Loss of galectin-3 expression in mucinous colorectal carcinomas is associated with 5'CpG island methylation in Tunisian patients.

The ß-galactoside-binding protein galectin-3 (gal-3) has pleitropic biological functions and has been implicated in cell growth, differentiation, adhesion, RNA processing, apoptosis, and malignant transformation. To investigate the pattern of inactivation of the gal-3 gene (LGALS3) in colorectal cancers (CRC), we studied a series of Tunisian patients with CRC to identify abnormal methylation in LGALS3 promoter using a methylation-specific PCR. We also examined the gal-3 gene expression by reverse transcription-PCR and the expression of gal-3 protein by immunohistochemistry. Analysis of DNA methylation in nonmucinous colorectal carcinomas expressing gal-3 protein showed an unmethylated profile of LGALS3 promoter, whereas gal-3 was aberrantly methylated in mucinous colorectal carcinomas. Complete loss of the gal-3 expression both at mRNA and the protein level was associated with the gal-3 methylation in the mucinous colorectal carcinomas. Our results show that methylation of the gal-3 promoter could be an important mechanism in the regulation of the expression of this gene in mucinous CRCs.

Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients.

We examined the association of one linked GC/AT polymorphism at p73 with the risk of colorectal cancer. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. The p73 genotypes were determined by PCR-restriction fragment length polymorphism in 150 Tunisians patients with colorectal cancer and in 204 healthy control subjects. Immunohistochemistry was performed on normal mucosa, primary tumour and metastasis. The frequencies of the genotypes were 52% for wild-type (GC/GC), 31% for heterozygotes (GC/AT) and 17% for variants (AT/AT) in patients, and 54%, 35% and 11% in controls, respectively. There were no significant differences of the frequencies of the three genotypes between the patients and controls (p = 0.11). We did not find any relationship of the genotypes with clinicopathological features of patients. We found that patients with the AT/AT genotype had a significantly worse clinical outcome than those with the GC/AT and GC/GC genotype. There were no significant differences between tumoural immunostaining of the total p73 and p73 polymorphism (p = 0.16). However, we found a significant difference between the expression profile of DeltaNp73 isoform and frequencies of the three genotypes (p = 0.0001). No LOH was observed at p73 locus. Our results suggest that the AT/AT genotype is significantly associated with poor prognosis in colorectal cancer. All these findings suggest that p73 polymorphism analysis may provide useful prognostic information for colorectal cancer patients.

[Epidemiological study, pathologic evaluation and prognostic factors of colorectal mucinous vs non-mucinous adenocarcinoma (a series of 196 patients)]. / Etude épidémiologique, anatomopathologique et évaluation des facteurs pronostiques des adénocarcinomes colorectaux mucineux vs non mucineux. (A propos d'une série de 196 patients).

BACKGROUND: Colorectal carcinoma is one of the main causes of cancer death in the worldwide with a decrease survival rate in relationship with a later diagnosis of advanced disease. AIMS: This study highlights the particular epidemiological, clinicopathological and immunohistochemical colorectal cancer profile. Indeed, our results differ markedly from that reported in the literature. METHODS: We underwent a retro and prospective study interesting 196 patients with colorectal carcinoma diagnosed in the pathological and cytological laboratory of Mongi Slim Hospital (Tunisia). Age at diagnosis, mode of presentation, sex, tumour location, macroscopic and histological features, TNM and Astler Coller stage were assessed and evaluated. RESULTS: We report here a particular epidemiological pattern which is characterised by younger age of the patients, equally distribution between men and women, predominant sporadic carcinomas and preponderance of rectosigmoid location. The poorer degree of differentiation and mucinous subtype are correlated with an advanced stage. It is also correlated with more frequent vascular embols, neural invasion and metastatic nodes. Furthermore, immunohistochemical analysis of galectin-3 showed a significant difference between mucinous and non mucinous adenocarcinoma. CONCLUSION: Based on the presented data, the epidemiological pattern and the anatomic distribution especially in the rectosigmoid region suggest diet and lifestyle to be primordial risk factors of colorectal tumorigenesis.

The prognostic value of p73 overexpression in colorectal carcinoma: a clinicopathologic, immunohistochemical, and statistical study of 204 patients.

INTRODUCTION: The protein p73 is the first identified homolog of the tumor suppressor gene p53, but its function in tumor development has not been established. Indeed, the results regarding the p73 implication in colorectal cancers is still controversial. AIM: We investigated whether the p73 is implicated in colorectal cancer, whether the p73 expression is related to prognosis and whether the p73 expression is correlated with p21-ras or p53. MATERIALS AND METHODS: We performed a comparative immunohistochemical analysis of p73, p53, and p21ras proteins in primary colorectal tumor with matched normal mucosa and metastasis from 204 patients with colorectal cancer. We correlated these expressions with clinicopathologic variables and we compared the different profiles between nonmucinous carcinoma and mucinous carcinoma. RESULTS: In this study, we did not find any correlation between p73 expression, sex, age, site, differentiation and stage. Overexpression of p73 was significantly correlated with infiltrating growth pattern (P<0.0001) and nonmucinous carcinoma (P<0.0001). Furthermore, frequency and intensity of p73 expression were marquedly increased from normal mucosa (26%), to primary tumors (75%) and to metastasis (97%). Furthermore, expression of p73 was also correlated with shorter survival period. The prognostic significance of p73 expression remained, even after adjustment for the clinical and pathologic variables. The p73 expression was positively correlated only with p21ras expression (P<0.0001). CONCLUSIONS: All these findings prove that p73 expression should be considered as a valuable poor prognostic marker. Our data also suggest that TP73 gene may play a role in colorectal carcinoma development.