Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.

Clinicopathological significance of cancer stem cell markers CD44 and ALDH1 expression in breast cancer.

BACKGROUND: CD44 and aldehyde dehydrogenase 1 (ALDH1) has been reputed to be cancer stem cell (CSC) markers in breast cancer. Yet, the clinicopathologic and prognostic significance of these markers remain unclear. In this study, we have investigated the expression of these markers and their relation with conventional clinicopathologic tumor characteristic including molecular subtype. METHODS: CD44 and ALDH1 expression were investigated by immunohistochemistry in a series of 157 formalin-fixed paraffin-embedded breast cancer tissues. RESULTS: Overall, CD44 and ALDH1 are, respectively, detected in 33% (52 of 157) and 7% (10 of 157) of breast cancer cases. We also observed that CD44 expression was associated with histological grade (p = 0.005). For ALDH1, we found that its expression is more frequent with elderly women (> 50 years, p = 0.03). The investigation of relationship between the stem cell phenotype and breast cancer molecular subtype, revealed that CD44 and ALDH1 expression was more frequent in basal-like tumors (p = 0.005). Among the two cancer stem cell markers tested, ALDH1 showed a strong association with the basal marker EGFR (p = 0.05). CONCLUSIONS: These findings suggest that CD44 and ALDH1 play a role in the clinical behavior in breast cancer and might be interesting biomarkers and therapeutic targets.

Gastric Adenocarcinomas in Central Tunisia: Evolution Specificities through Two Decades and Relation with Helicobacter pylori.

INTRODUCTION: In developed countries, authors have reported variations over time in the seat and histological type of gastric adenocarcinomas, which were explained by Helicobacter pylori infection (HPI) incidence changes. In North-African countries and the Arabic world, epidemiological changes in gastric adenocarcinomas are still unknown. Our study aims to explore and to describe those changes in central Tunisia. MATERIALS AND METHODS: This is a retrospective observational and descriptive study including 876 cases based on the National Central Tunisian Register of Cancers over a period of 21 years. Two groups were formed and compared (group A: 337 patients from 1995 to 2005; group B: 539 patients from 2006 to 2015). RESULTS: HPI decreased from 32.6% in group A to 11.2% in group B (p < 0.05). Signet ring cell carcinomas increased in 2 decades from 14% in group A to 36% in group B (p < 0.05). Proximal cancers were 16.61% in group A and increased to 19.66% in group B (p = 0.3). Total gastrectomy rate was 10.4% in group A versus 23.2% in group B (p < 0.05). CONCLUSION: This study has shown a significant increase of signet ring cell carcinomas with a simultaneous decrease in HPI in the last decade in central Tunisia.

The Bethesda System for Reporting Thyroid Cytopathology Explained for Practitioners: Frequently Asked Questions.

BACKGROUND: The recent update of The Bethesda System for Reporting Thyroid Cytology (TBSRTC) is a very important development in the evaluation of thyroid nodules. Clinical experience and scientific literature both show that practitioners performing thyroid fine-needle aspiration are accustomed to basing the clinical management of patients on reports using TBSRTC. Specifically, clinicians are familiar with the percent risk of malignancy corresponding to each TBSRTC diagnostic category (DC), as well as with the respective recommendation for clinical management. However, most clinicians are much less familiar with the specific considerations that lie between a given DC, on the one end, and the respective risk of malignancy and associated management recommendation, on the other end. SUMMARY: A deeper understanding of the system can enlighten the clinician's thinking about the specific nodule under examination and can guide the decision-making process in a more meaningful way. Such an understanding can only be developed via close two-way communication between cytopathologists and clinicians. Through this type of interaction in the authors' tertiary medical center, recurring issues of particular importance for clinical practice were identified, which are reported here in the form of 16 frequently asked questions posed by the clinician to the cytopathologist. CONCLUSIONS: For each frequently asked question, an answer is provided based on the literature, the authors' experience, the new version of TBSRTC, and the new World Health Organization classification of tumors of endocrine organs.

Stromal CD10 expression in breast cancer correlates with tumor invasion and cancer stem cell phenotype.

BACKGROUND: Previous investigations have indicated that CD10 is associated with biological aggressivity in human cancers, but the use of this marker for diagnosis and prognosis is more complex. The aim of this study was to evaluate the expression of CD10 in breast cancer and its association with the clinicopathological features. In addition, we investigated whether a relationship exists between CD10 expression and cancer stem cells. METHODS: CD10 expression was examined by the immunohistochemistry in a series of 133 invasive breast carcinoma cases. Results were correlated to several clinicopathological parameters. Cancer stem cell phenotype was assessed by the immunohistochemical analysis of CD44 and ALDH1. RESULTS: Significant CD10 expression was found in the fusiform stromal cells in 19.5% of the cases and in the neoplastic cells in 7% of the cases. The stromal CD10 positivity was more frequently found in tumors with lymph node metastasis (p = 0.01) and a high histological grade (p = 0.01). However, CD10 expression by the neoplastic cells correlates with a high histological grade (p = 0.03) and the absence of estrogen (p = 0.002) as well as progesterone (p = 0.001) receptor expression. We also found that CD10 expression by the stromal cells, but not by the neoplastic cells, correlates significantly with the expression of cancer stem cell markers (CD44+/ALDH1+) (p = 0.002). CONCLUSION: These findings support the role of the stromal CD10 expression in breast cancer progression and dissemination, and suggest a relationship with cancer stem cells.

Vaginal Enterobius vermicularis diagnosed on liquid-based cytology during Papanicolaou test cervical cancer screening: A report of two cases and a review of the literature.

Enterobiasis is one of the most common human parasitic infections. It is considered an intestinal parasite, but cases of extra-intestinal affections exist, notably infections of the female genital tract. Enterobius vermicularis (EV) eggs (or ova) have been found in the cervical smears of two patients in our institute during the last 16 years. No gynaecological or gastrointestinal symptoms were reported, and there was no known intestinal infection in these two cases. A review of the available literature revealed rare cases of vaginal enterobiasis, with a wide range of clinical presentations, many patients being asymptomatic. The diagnosis may sometimes be difficult, mainly because of the lack of clinical suspicion. However, cytological identification of EV in cervico-vaginal smears is important, especially when considering the risk of ascending infections of the genital tract associated with severe complications.

Changing patterns in the Epstein-Barr virus (EBV)and Hodgkin lymphoma association in Tunisia.

We compared the features of the Epstein-Barr virus (EBV) and Hodgkin lymphoma (HL) association in Tunisia in two periods of time, 1991-2001 (111 cases) and 2002-2012 (122 cases). The investigation of the EBV status by EBER in situ hybridization showed a significant decrease in the prevalence of EBV-positive HL from 69.3 % for the period 1991-2001 to 40.1 % for the 2002-2012 period (p = 0.00001). EBV positivity has decreased in all age groups but was more pronounced among young patients, in the 15-24-year age group (46.1 vs 10.3 %, p = 0.003), in the 25-34-year age group (56.2 vs 25 %, p = 0.04), and among children (88.4 vs 59.2 %, p = 0.01). This decrease in EBV-positive HL over time contrasted with a remarkable increase in EBV-negative HL in young adults aged 15-34 years (51.2 vs 83 %; p = 0.001), especially among women (59.1 vs 91.2 %; p = 0.01). The decrease in EBV-positive HL over time concerns particularly the nodular sclerosis histological subtype (69.2 vs 31.6 %, p = 0.000001). These results indicate that the epidemiology of HL and its association with EBV are changing over time, with a trend toward a Western profile, and point toward the emergence of other environmental causative factors, especially among young women, which remain to be identified.

DNA methylation patterns in EBV-positive and EBV-negative Hodgkin lymphomas.

PURPOSE: Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells. Epstein-Barr virus (EBV) infection is thought to play an important role in the development of HL. Although epigenetic alterations, such as aberrant DNA methylation, are known to contribute to the pathogenesis of various malignancies, little is known about such alterations in HL and their putative relationships with EBV infection. METHODS: We investigated promoter methylation patterns of seven tumor-associated genes in 53 primary HL cases using methylation-specific PCR (MS-PCR). Concomitantly, the EBV infection status was assessed using PCR, in situ hybridization and immunohistochemistry. RESULTS: The gene promoter hypermethylation frequencies observed were 77.3 % for P16, 58.5 % for RASSF1A, 50.9 % for CDH1, 45.3 % for DAPK, 43.4 % for GSTP1, 37.7 % for SHP1 and 24.3 % for MGMT. SHP1 gene promoter hypermethylation was more frequently observed in patients at extreme ages (i.e., ≤ 15 and >54 years) than in adult patients (p = 0.006) and in patients with B symptoms (p = 0.03). Interestingly, most of the analyzed gene promoters were more frequently hypermethylated in EBV-negative than in EBV-positive cases, in particular the DAPK gene promoter (58 % versus 27 %, p = 0.04). Furthermore, hypermethylation of multiple gene promoters (≥ 3) was encountered more frequently in females than in males (86 % versus 57 %, p = 0.04), whereas EBV-positive cases were more common among males than females (55 % versus 30 %, p = 0.02). CONCLUSIONS: Our results indicate that epigenetic changes frequently occur in both EBV-positive and EBV-negative HL. The rates of these changes were found to vary according to clinico-pathological parameters. These observations probably reflect the multitude of factors involved in HL development and the complexity of their interactions with genetic and/or hormonal factors.

Investigation of miR9-1, miR9-2 and miR9-3 Methylation in Hodgkin Lymphoma.

BACKGROUND: miR9 is an important tumor suppressor microRNA regulated by DNA methylation in various types of cancers. METHODS: We analyzed the methylation status of the 3 members of the miR9 family in 58 cases of Hodgkin lymphoma (HL) in comparison to 15 reactive lymph nodes. We also assessed the relationships between miR9 methylation and Epstein-Barr virus (EBV) infection and several clinicopathological parameters. RESULTS: We found that 84.5% of HL cases had a methylation in at least 1 of the 3 loci of miR9, whereas none of the nontumoral samples was methylated. The highest rate of methylation was found in miR9-2 (5q14.3) in 74.1% of the HL cases, followed by miR9-3 (15q26.1) in 56.9% and miR9-1 (1q22) in only 8.6% (p < 0.001). The promoter methylation of miR9-3 was more frequent in patients older than 15 years than in children (p = 0.02) and among women rather than men (p = 0.02). However, no significant correlation was found between miR9 methylation and EBV infection. CONCLUSION: These results indicate that miR9 methylation, especially miR9-2, is a frequent event in HL and may be involved in HL pathogenesis, irrespective of EBV infection.

Assessment and biological significance of JC polyomavirus in colorectal cancer in Tunisia.

PURPOSE: Several reports have indicated the presence of JC polyomavirus (JCV) in many human tumors, including colorectal cancers (CRCs). The presence of JCV infection in CRC patients has not been investigated in African countries. METHODS: We examined the prevalence and the biological significance of JCV in Tunisian CRC patients. The presence of JCV was assessed by polymerase chain reaction (PCR) in a series of 105 CRCs and 89 paired non-tumor colonic mucosa samples from Tunisian patients. Results were correlated with the clinicopathological features and immunohistochemical expression of ß-catenin, p53, and the proliferation marker Ki-67. RESULTS: JCV DNA was detected in 58.1% (61/105) of CRC and in only 14.6% (13/89) of paired non tumor colonic mucosa samples (p=0.03). The presence of JCV was significantly correlated with tumor differentiation (p=0.03). Moreover, JCV presence was significantly correlated with nuclear accumulation of ß-catenin (p=0.008) and p53 accumulation (p=0.0001). Multivariate logistic regression analysis showed that tumor differentiation, ß-catenin and p53 accumulation were independent parameters significantly associated with the presence of JCV in CRC (p=0.04; p=0.05; p=0.001, respectively). CONCLUSION: We support a role of JCV in colorectal carcinogenesis in Tunisian patients, especially of well differentiated morphology.

Increased DNA methyltransferase 1 protein expression correlates significantly with intestinal histological type and gender in gastric carcinomas.

PURPOSE: Promoter hypermethylation and reduced expression of many genes have been found in gastric cancer. DNA methyltransferases are enzymes potentially affecting promoter hypermethylation. MATERIAL AND METHODS: We analyzed proteins expression of DNA methyltransferase 1 and 3b by immunohistochemistry in 47 surgically resected gastric cancer samples for which clinicopathological characteristics, patient's outcome and methylation status of 11 selected tumor-related genes have been determined. Promoter methylation status of genes was assessed by methylation specific PCR. RESULTS: We found that DNMT1 and 3b were up-regulated in gastric cancer and were detected in 51.1% and 57.4% of cases, respectively. Co-expression of DNMT1 and 3b was detected in 44.7%. Correlations analysis have showed that DNMT1 overexpression was significantly correlated with gastric cancer of intestinal histological type (P=0.01) and with gender of patient (P=0.01). However, there was no correlation between DNMT1 and DNMT3b overexpression in cancer and patients outcome. Moreover, there were no clear relations between the proteins expression of DNMT1 and 3b and DNA methylation status of genes. But co-expression of DNMT1 and DNMT3b was significantly associated with promoter hypermethylation of RAR-ß2 (P=0.04). CONCLUSIONS: Results from our study indicate that DNMT1 and 3b were overexpressed and could be involved in gastric tumorigenesis of intestinal histological type in the case of Tunisian patients.

Expression of topoisomerase II alpha, ki67, and p53 in primary non-muscle-invasive urothelial bladder carcinoma.

To assess the prognostic value and clinicopathological correlate of the expression of topoisomerase II alpha, ki67, and p53 in non muscle-invasive urothelial bladder carcinoma. Seventy one cases of formalin-fixed, paraffin-embedded bladder biopsy specimens diagnosed as non muscle invasive urothelial carcinoma were processed by searching our surgical pathology files from 2001-2003. The patients were followed-up for 3-77 months (median = 28). In each case, one tissue block was chosen for immunohistochemical expression of ki67, topoisomerase II alpha and p53. This expression was associated with the pathological stage, grade, recurrence, progression and survival. Positive staining of topoisomerase II alpha, ki67, and p53 was found respectively in 39.5, 38, and 38% cases. We have found a statistically significant correlation between the expression of each of the 3 markers and WHO grade and recurrence. The surexpression of topoisomerase II alpha was associated within increased tumor stage. p53 was associated with tumor progression. On multivariate analysis, p53 was an independent factor of progression into muscle-invasive tumors and none of these markers had predictive value on recurrence. The present findings support the clinical relevance of these markers in bladder cancer.

Methylation of miR-124a-1, miR-124a-2, and miR-124a-3 genes correlates with aggressive and advanced breast cancer disease.

Aberrant DNA methylation on CpG islands is one of the most consistent epigenetic changes in human cancers, and the process of methylation is catalyzed by the DNA methyltransferases DNMT1, DNMT3a, and DNMT3b. Recent reports demonstrate that deregulation of miR-124a, one of the frequently methylated microRNAs in human cancers, is related to carcinogenesis. The aim of this study was to evaluate the frequencies of methylation of the three genomic loci encoding the miR-124a in primary breast cancers and to investigate their relationships with the clinicopathological characteristics of the tumors and with the expression levels of DNMT1, DNMT3a, and DNMT3b. The methylation status of the three genomic loci encoding the miR-124a (miR-124a-1, miR-124a-2, and miR-124a-3) was analyzed in fresh-frozen tumor samples using methylation-specific PCR in a large series of invasive breast ductal carcinomas (n = 60). Results were correlated to several clinicopathological characteristics of the tumors and to the expression levels of DNMT1, DNMT3a, and DNMT3b, determined by immunohistochemistry. Promoter hypermethylation of miR-124a-1, miR-124a-2, and miR-124a-3 was detected in 53.3, 70, and 36.7% of cases, respectively. Methylation of miR-124a-2 correlated to patients with age higher than 45 years (P = 0.008) and to postmenopausal patients (P = 0.03), whereas methylation of miR-124a-3 correlated significantly to tumor size >20 mm (P = 0.03). Interestingly, simultaneous methylation of the three genes encoding miR-124a correlated significantly with the presence of lymph node metastasis (P = 0.01) and high mitotic score (P = 0.03). No significant correlation was found between promoter hypermethylation of miR-124a and expression of hormone receptors or HER2/neu. With regard to DNMT expression, no correlation was found between DNMT1 or DNMT3a expression and promoter methylation of any tested microRNA. However, DNMT3b overexpression correlates significantly with the hypermethylation of miR-124a-3 (P = 0.03). Our data indicates that miR-124a-1, miR-124a-2, and miR-124a-3 genes are frequently methylated in breast cancer and play a role in tumor growth and aggressivity.

Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers.

DNA methyltransferase 1, 3a, and 3b affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. The current study was designed to analyze DNA methyltransferase expression by immunohistochemistry in a series of 94 Tunisian sporadic breast carcinomas. Results were correlated to clinicopathologic parameters and promoter methylation status of 8 tumor suppressor genes (BRCA1, BRCA2, RASSFA1, TIMP3, CDH1, P16, RARß2, and DAPK). Overexpression of DNA methyltransferase 1, 3a, and 3b was detected in 46.8%, 32%, and 44.7% of cases, respectively. A significant correlation was found between DNA methyltransferase 1 overexpression and Scarff-Bloom-Richardson histologic grade III (P = .01). DNA methyltransferase 3a overexpression was significantly associated with menopausal status (P = .01), Scarff-Bloom-Richardson histologic grade III (P = .0001), estrogen (P = .04) and progesterone (P = .007) receptor negativity, and HER2 overexpression (P = .004). However, DNA methyltransferase 3a overexpression was found less frequently in the luminal A intrinsic breast cancer subtype (9.7%) than in luminal B (53%), HER2 (41%), and triple-negative (50%) subtypes (P = .001). DNA methyltransferase 3b overexpression shows significant correlation with promoter hypermethylation of BRCA1 (P = .03) and RASSFA1 (P = .04) and with the hypermethylator phenotype (more than 4 methylated genes, P = .01). These data suggest that overexpression of various DNA methyltransferases might represent a critical event responsible for the epigenetic inactivation of multiple tumor suppressor genes, leading to the development of aggressive forms of sporadic breast cancer.

Investigation of human JC and BK polyomaviruses in breast carcinomas.

We have previously showed the presence of the simian virus 40 (SV40) and the mouse mammary tumor virus (MMTV)-like in a significant proportions of Tunisian breast carcinomas. However, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses JC (JCV) and BK (BKV) in breast carcinomas. The presence of JCV and BKV DNA was investigated by PCR in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. The results were correlated to clinicopathological and virological parameters. JCV T-antigen DNA was detected in 23% of breast carcinoma cases; however, all cases were negative for BKV. JCV T antigen PCR products were further confirmed as authentic JCV genome by direct sequencing. JCV was found in invasive ductal carcinomas (28/112 cases) but not in invasive lobular carcinomas (0/5) or medullary carcinomas (0/6). JCV DNA presence correlates inversely with the expression of estrogen (P = 0.022) and progesterone (P = 0.008) receptors. JCV DNA presence correlates also with "triple negative" phenotype (P = 0.021). With regard to virological data, a trend toward an inverse correlation was noted between the presence of JCV and SV40 (P = 0.06). Moreover, significant correlation was found between multiple viral infection (JCV, and/or SV40, and/or MMTV-like in the same tumor) and "triple negative" phenotype (P = 0.001) and also with p53 accumulation (P = 0.028). To the best of our knowledge, this is the first study demonstrating the presence of JCV in a subset of breast carcinomas. Also our results suggest that "triple negative" breast carcinomas are viral-related tumors.

Investigation of Epstein-Barr virus in breast carcinomas in Tunisia.

Breast carcinoma is a major cause of death among women, and the potential implication of viruses in its pathogenesis remains worth a hypothesis. The potential role of Epstein-Barr virus (EBV) in its pathogenesis is still a subject of continued discussion and investigation. The aim of this study was to evaluate the prevalence of EBV in sporadic breast cancers in Tunisia, and to determine the clinicopathological characteristics of virus-positive cases. Viral presence has been evaluated by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry investigated on tumor tissues and their corresponding normal breast tissues collected from 123 Tunisian women with sporadic breast carcinomas. Viral status in tumors was then correlated with various clinicopathological parameters. Using specific PCR assays, EBV DNA was found in 33 (27%) out of 123 breast carcinoma cases. EBV-encoded small RNAs (EBERs) in situ hybridization was negative in the neoplastic cells, but stomal lymphocytes were positive in 4 cases. Immunohistochemistry for latent membrane protein 1 (LMP1) was negative in all cases. None of the normal breast tissues showed positive results for EBV using PCR, in situ hybridization, and immunohistochemistry. A correlation was found between EBV DNA presence and the negativity of estrogen receptor (P=0.008). However, no significant correlation was found for the other parameters investigated, including patient age, Scarff-Bloom-Richardson (SBR) histological grade, tumor size, and histological node involvement. With regard to survival data, overall and disease-free survivals were shorter in EBV-positive breast carcinoma cases than in EBV-negative ones, but this difference did not reach statistical significance. Our study indicates the presence of EBV DNA in a significant proportion of breast cancer in Tunisia. Further studies are required to elucidate the role of this virus in breast carcinogenesis.

Tumeur myofibroblastique inflammatoire de la vessie.

La tumeur myofibroblastique inflammatoire est une lésion classée par l'OMS parmi les néoplasies intermédiaires. Elle peut siéger dans différents organes : les poumons, le pancréas, le mésentère et l'utérus. La localisation vésicale est rare.Nous rapportons le cas d'un jeune homme de 38 ans qui a consulté pour hématurie. L'échographie a révélé la présence d'une structure tissulaire intravésicale de 3 cm de grand axe. L'examen anatomopathologique et l'étude immunohistochimique ont conclu à une tumeur myofibroblastique inflammatoire de la vessie. À partir de cette observation, nous présentons les diagnostics différentiels et les particularités anatomopathologiques de cette localisation rare.Myofibroblastic inflammatory tumor is considered as an intermediate neoplasm according to the WHO classification. It can occur in different organs: lung, pancreas, mesentery and uterus. The localization in the bladder is unusual. We report a case of a 38-year-old patient who presented with hematuria. Echography showed a 3 cm tissular structure of the bladder. Histological analysis and immunohistochemistry concluded to the diagnosis of myofibroblastic tumor of the bladder. The present work will give a general view of the myofibroblastic tumor, and will review its differential diagnosis.

[Utility of immunohistochemistry in detecting alterations of mismatch repair genes of DNA. A series of 48 cases of colorectal cancer]. / Utilité de l'immuno-histochimie dans la détection des altérations des gènes réparateurs des mésappariements de l'ADN À propos d'une série de 48 cas de cancers colorectaux.

Hereditary non-polyposis colorectal cancer (HNPCC) is associated in more than 95% to a germline mutation in the genes of the mismatch repair (MMR) of DNA. The aim of this study was to assess the utility of immunohistochemistry, a simple and fast technique, in the triage of families where HNPCC is suspected. Tumor samples included in this study were from patients with resection for colorectal cancer, examined in our laboratory between 2004 and 2007. For each case, a formalin-fixed paraffin-embedded tissue block containing tumor tissue and normal adjacent mucosa was selected. Tumor specimens were examined with immunohistochemistry for the presence of hMLH1, hMSH2, and hMSH6 proteins. Scoring of the tumor staining was performed without any knowledge of patients' family history. The loss of protein expression was noted in four patients among 48 cases tested: two cases with isolated loss of hMSH2, a case with isolated loss of hMSH6 and one case with combined loss of MSH2/MSH6. No case has shown a suppression of hMLH1 protein. Comparing the immunohistochemical results for clinical has revealed a clear correlation between loss of protein expression demonstrated by immunohistochemistry and clinical data. Indeed, three cases among the four who showed no expression of MMR proteins showed at least one clinical criterion predictive of HNPCC. In conclusion, our study support the potential utility of immunohistochemistry to identify a significant portion of colorectal tumors derived from germline mutation of MMR genes and can be used as an adjunct measure in the identification of HNPCC.