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.

[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.

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.

Cervical adenocarcinoma and squamous cell carcinoma incidence trends among Tunisian women.

INTRODUCTION: Uterine cervix cancer is an important public health problem in Tunisia. In this study, we report trends in the incidence of adenocarcinoma and squamous cell carcinoma of the cervix uteri in the central region of Tunisia during 1993-2006. DESIGN: Data were obtained from the Cancer Registry of the Center of Tunisia which registers invasive cancer cases by active methods. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual population data. RESULTS: Among all women cancers, cervix uteri cancer accounted for 5.9% and ranked the fourth during the study period with an ASR of 6.9 per 100,000. The ASRs decreased notably with an APC of -6.7% over the whole period. However, incidence rates of adenocarcinomas have increased during the last years (APC: +14.4%). CONCLUSION: The introduction of cytological screening programs has led to a marked decrease of the incidence rates of cervix uteri cancer among Tunisian women. The data underline the fact that the population-based cancer registry is an indispensable tool for providing data for planning and evaluation of programs for cancer control.

Cervix cancer in Tunisia: clinical and pathological study.

INTRODUCTION: Uterine cervix cancer is the second most commonly diagnosed cancer among women worldwide. DESIGN: In order to review the clinical and pathological features of cervix cancer in the center of Tunisia, a retrospective study was carried out on 410 cancer cases diagnosed in the Pathology Department, Farhet Hached University Hospital, Sousse, Tunisia (1993-2006). RESULTS: The mean age was 52.1 years. Of the 410 patients, 90.5% had squamous cell carcinoma and 7.3% had adenocarcinoma. One hundred thirty-eight patients were identified as being in early stages (0 and I) (33.6%) and 58.2% in advanced stages (II-IV). Therapy consisted mainly in combination of radiotherapy and surgery in early stages (28.8%), and radiotherapy alone or associated with the chemotherapy in advanced stage (29.7%). Surgery was the only treatment in 29.5% of cases. CONCLUSION: A relatively large proportion of patients presented in stages II to IV, as compared to only 36% with early stages, emphasizing the need to reinforce the early detection of this cancer and its precursor lesions in the center of Tunisia.

Trends in the incidence of cancer in the Sousse region, Tunisia, 1993-2006.

In this article, we analyzed trends in incidence rates of the major cancer sites for a 14-year period, 1993-2006, in the Sousse region localized in the centre of Tunisia. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size and its estimated age structure. A total of 6,975 incident cases of cancer were registered, with a male to-female sex ratio of 1.4:1. ASRs showed stable trends (-0.1% in males, and +1.0% in females). The leading cancer sites in rank were lung, breast, lymphoma, colon-rectum, bladder, prostate, leukemia, stomach and cervix uteri. For males, the incidence rates of lung, bladder and prostate cancers remained stable over time. While, cancers of colon-rectum showed a marked increase in incidence (APC: +4.8%; 95% CI: 1.2%, 8.4%) and non-Hodgkin's lymphoma (NHL) showed a notable decline (APC: -4.4%; 95% CI: -8.2, -0.6). For females, cancers of the breast (APC: +2.2%; 95% CI: 0.4%, 4.0%) and corpus uteri (APC: +7.4%; 95% CI: 2.8%, 12.0%) showed a marked increase in incidence during the study period, while the cervix uteri cancer decreased significantly (APC: -6.1%; 95% CI: -9.2%, -3.0%). The results underline the increasing importance of cancer as a cause of mortality and morbidity in Tunisia. Our findings justify the need to develop effective program aiming at the control and prevention of the spread of cancer amongst Tunisian population.

No evidence of human papillomavirus DNA in breast carcinoma in Tunisian patients.

The aim of this study was to evaluate the prevalence of broad range of anogenital HPVs in a series of 123 Tunisian breast carcinoma cases. PCR assays were performed to amplify regions within the L1, E1, E6 and E7 open reading frames of a broad range of anogenital HPVs and specific types HPV16, 18, 31 and 33. In addition, we performed an in situ hybridization analysis using HPV biotinylated DNA probes for the detection of broad spectrum of anogenital HPV types, high-risk HPV types (16 and 18), intermediate-risk HPV types (31 and 33) and low-risk HPV types (6 and 11). None of the 123 breast carcinoma samples showed PCR amplification of HPV DNA using the broad spectrum consensus primer-pairs E1-350L/E1-547R and GP5+/GP6+ primers. Furthermore, neither high risk nor low-risk HPV types were detected in any of these cases. Moreover, using in situ hybridization for the detection of HPVs, we failed to detect a positive signal in neoplastic cells in any case. Our results suggest that anogenital papillomaviruses are unlikely to play a role in the development of breast carcinomas in Tunisian patients.

[Prevalence of HPV infection in precancerous and cancerous lesions of the uterine cervix in Tunisia]. / Prévalence des infections à papillomavirus (HPV) dans les lésions précancéreuses et cancéreuses du col utérin en Tunisie.

OBJECTIVES: To investigate the distribution of HPV genotypes inuterine cervical lesions in Central Tunisia in order to predict the impact ofHPV vaccines and HPV-based screening tests among Tunisian women. MATERIAL AND METHODS: We performed a retrospective study of 146 fixed tissues including 30 benign lesions, 36 low-grade cervical intraepithelial neoplasias (CIN1), 45 high-grade cervical intraepithelial neoplasias (CIN2/3), 26 invasive squamous cell carcinomas (SCC) and 9 adenocarcinomas. HPV infection detection and typing were investigated by PCR technique using consensus GP5/GP6 primers and type specific primers for HPV6/11, 16, 18, 31 and 33. RESULTS: Among our patients, overall HPV prevalence was 73.6% (p = 0.0001). HPV infection was associated to 84% of precancerous lesions and 83.9% of cancers. High-risk HPV infection (HPV16 and 18) was detected in 17.4% of CIN1, 74.3% of CIN2/3 (p = 0.002) and 73.1% of cancers (p = 0.001). HPV16 was the most common type among CIN2/3 (51.2%, p < 0.001), invasive SCC (47.6%, p = 0.001) and adenocarcinomas (80%, p < 0.001). CONCLUSION: This study supports previous population-based studies in which similar HPV detection rates were found among random samples of women. HPV-based screening tests and HPV vaccination would be efficient in uterine cervix cancer prevention among women in the Central Tunisia.

DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) are the most common type of aggressive lymphomas, with considerable heterogeneity in clinical presentation, molecular characteristics, and outcome. Previous studies have showed significant correlations between DNA methyltransferase (DNMT) overexpression and unfavorable prognosis in human cancers. Therefore, we investigated in this study the biological and prognostic significance of DNMT1, DNMT3a, and DNMT3b protein expression in DLBCL. DNA methyltransferase (DNMT) expression was analyzed by immunohistochemistry in 81 DLBCL cases and correlated with clinicopathological parameters. Kaplan-Meier curves were used to estimate survival rates, and the Cox proportional hazard regression model was used to evaluate the prognostic impact of DNMT expression. Our results showed that overexpression of DNMT1, DNMT3a, and DNMT3b were detected in 48%, 13%, and 45% of investigated cases, respectively. DNA methyltransferase 1 (DNMT1) and DNMT3b overexpression was significantly correlated with advanced clinical stages (P = 0.028 and P = 0.016, respectively). Moreover, concomitant expression of DNMT1 and DNMT3b was significantly correlated with resistance to treatment (P = 0.015). With regard to survival rates, although data was available only for 40 patients, DNMT3b overexpression was significantly correlated with shorter overall survival (P = 0.006) and progression-free survival (P = 0.016). Interestingly, multivariate analysis demonstrated that DNMT3b overexpression was an independent prognostic factor for predicting shortened overall survival (P = 0.004) and progression-free survival (P = 0.024). In conclusion, DNMT3b overexpression was identified as an independent prognostic factor for predicting shortened survival of patients with DLBCL and could be, therefore, useful in identifying patients who would benefit from aggressive therapy.

p16INK4A overexpression in precancerous and cancerous lesions of the uterine cervix in Tunisian women.

Uterine cervix cancer is an important public health problem in developing countries. However, there is a substantial lack of inter-observer diagnostic reproducibility for its precursor lesions (CIN1). The study was performed to evaluate the usefulness of p16(INK4A) overexpression as a surrogate marker for uterine cervix precancerous lesions and high-risk human papillomavirus (HPV) infection. We conducted a retrospective study of 87 uterine cervix specimens, including 7 normal tissue samples, 17 benign lesions, 34 precancerous lesions, 22 invasive squamous cell carcinomas (SCC), and 7 adenocarcinomas. Immunohistochemistry was used to find p16(INK4A) overexpression. HPV infection was detected by PCR. No immunoreactivity for p16(INK4A) was detected in normal tissue or benign lesions. p16(INK4A) immunoreactivity was focal in CIN1, whereas strong and diffuse immunoreactivity for p16(INK4A) was uniformly observed in both the nucleus and the cytoplasm of all CIN2 and 3, as well as in those of invasive SCC and adenocarcinomas. A statistically significant association was observed between p16(INK4A) overexpression, lesion grade, and high-risk HPV infection (p<0.0001). p16(INK4A) overexpression is a useful additional marker for the interpretation of problematic uterine cervical lesions and can help to reduce the variability during evaluation of suspicious biopsies of the uterine cervix.

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes.

JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

Bilateral proliferating Brenner tumor of the ovary associated with recurrent urothelial carcinoma of the urinary bladder.

CONTEXT: Brenner tumors of ovary are relatively uncommon neoplasm. Most of them are benign and less than 5% are proliferating or borderline. The association between Brenner tumor of the ovary and papillary urothelial carcinoma of bladder is extremely rare. CASE REPORT: We describe an unusual case of proliferating bilateral Brenner tumor of the ovary with a highly recurrent low-grade papillary urothelial carcinoma of bladder. CONCLUSION: The immunohistopathological similarities of ovarian and bladder tumors and their association in the current case, may be coincidental but may reflect a common initiating event inducing similar pathogenesis changes in the epithelium of both organs. More cases are needed to be reported to better understand this association.

Squamous cell carcinoma arising from an epidermal inclusion cyst: A case report.

CONTEXT: Cutaneous epidermal cysts are common lesions, but fortunately, malignant transformation of their epithelium is rare. There are few case reports in the literature concerning malignant transformation of an epidermal cyst into squamous cell carcinoma. We present a case of squamous cell carcinoma arising from an epidermal inclusion cyst and describe the clinical and histopathologic findings. CASE REPORT: A tumour measuring 1.5cm was surgically excised. Based on the histopathologic findings of the tumour, this case was diagnosed as squamous cell carcinoma that arises in an epidermal cyst. Malignant change had not been suspected until histological examination revealed it. Nine months after tumour resection, the patient is free of disease. CONCLUSION: malignant transformation of an epidermal inclusion cyst is rare; this case illustrates the importance of routine histology in excision of epidermal cysts.

Primary Subcutaneous Ewing Sarcoma Presented as Pseudo Aneurysmal Subcutaneous Tumor.

BACKGROUND: Extraskeletal Ewing's sarcoma is a rare malignant tumor of mesenchymal origin, which is histologically similar to primary osseous Ewing's sarcoma. It has been well described in deep soft tissues. However, location in cutaneous or subcutaneous tissue has rarely been reported. Being seen principally in children, it can be seen, rarely, in old men. CASE REPORT: We present a case of subcutaneous Ewing sarcoma within the left shoulder of a 49-year-old man, without osseous involvement. Physical examination suggested a vascular tumor. Histologically, it was a small round cell tumor that marked strongly for CD99. The diagnosis of subcutaneous Ewing sarcoma was performed. CONCLUSION: Ewing sarcoma is a rare malignant small round cell tumor of the skin and subcutaneous tissue. It should be differentiated from other cutaneous neoplasms composed of small round cells.

Retroperitoneal Inflammatory Myofibroblastic Tumor: Case Report and Immunohistochemistry Study.

Inflammatory myofibroblastic tumors (IMT) are a rare clinicopathological entity of yet unknown etiology and those located retroperitoneally are even rarer. Clinical outcome is unpredictable and complete surgical resection of the tumor remains the principal treatment. We report the case of a 41-year old man presented with abdominal pain. An abdominal magnetic resonance imaging scan revealed a retroperitoneal tumor located between the pancreas, stomach small curvature and big vessels. A laparotomy with biopsy was performed because the tumor was not amenable to surgical resection. Histopathological examination concluded to an IMT with overexpression of protein p53. Epstein-Barr virus and Human Herpesvirus-8 investigation was negative. Postoperative outcome was unfavorable.

Prevalence and characteristics of Epstein-Barr virus-associated gastric carcinomas in Tunisia.

OBJECTIVE: Epstein-Barr virus (EBV) has been linked to gastric carcinoma (GC) with worldwide geographical variations of prevalence ranging from 1 to 18% of cases. Investigations carried out in north Africa have shown that some EBV-associated types of cancers are common in this area. This study was taken to determine the prevalence of EBV-associated GC in Tunisia. METHODS: Ninety-six nonselected GC cases (male/female ratio 1.7/1, mean age 60.9 years, range: 20-88 years) were evaluated for the presence of EBV by polymerase chain reaction as well as by in-situ hybridization for EBV-encoded small RNAs (EBERs) and immunohistochemistry for LMP-1 and EBNA-2 expression. RESULTS: EBV was detected by polymerase chain reaction in 36% of cases, whereas EBERs were detected in the tumor cells in only four cases (4.1%). Immunohistochemistry for LMP-1 and EBNA-2 was negative in all cases. The mean age for patients harboring EBERs-positive GC was 55.7 years (range: 52-59 years). All EBERs-positive GC cases were males of advanced clinical stage (pT3-pT4). According to Lauren's classification, two cases were of diffuse histological type and two cases were of intestinal type. In three cases, the tumors have a proximal location and in the remaining case the tumor arises in the antrum. All EBV strains detected from EBV-associated GC were exclusively of type A and D, prototype F, and XhoI-maintained variant. CONCLUSION: We conclude that the prevalence of EBV-associated GC in Tunisia is low (4.1%), suggesting that this virus is not an important etiological factor in GC arising in north African populations. The clinicopathological profile of EBV-associated GC in Tunisia did not differ markedly from that found elsewhere.

[Lethal osteo-chondro-dysplasia: feto-pathological study of 32 cases]. / Les ostéochondrodysplasies létales: etude foetopathologique de 32 cas.

BACKGROUND: The lethal osteochondrodysplasias are rare, their prevalence is estimated at 1 per 10 000 births. Mostly have genetic determinism. AIMS: To describe the malformations and dysmorphic features in lethal osteochondrodysplasias METHODS: Our study involved 32 cases of lethal fetal Osteochondrodysplasias, collected over a period of 14 years in the pathological department of Sousse. RESULTS: Our series consisted of 23 foetuses from a medical termination of pregnancy, 6 newborns and 3 stillbirths. The mean age of mothers was 28 years old, consanguinity was observed in 61%. 3 cases of recurrence of the disease in three families were noted. The bone abnormalities were detected in antenatal ultrasonography in 25 cases (87%) and at birth in 7 cases. Ultrasound showed micromelia in all cases, a narrow chest in 5 cases and spina bifida in 3 cases. The feto-pathological exam, including a macroscopic examination, radiological and histological samples of bone, has allowed us, based on the International Classification of 2001 to classify the 32 cases of Osteochondrodysplasias in: 8 cases of Achondrogenesis type I (type Parenti-Fraccaro), 3 cases of Achondrogenesis type II (Langer Saldino), 9 cases of lethal osteogenesis imperfecta, 8 cases of thanatophoric dysplasia, 4 cases of Schneckenbecken dysplasia, 2 cases of Short rib polydactyly syndrome, Majewski type and 1 case of asphyxiating thoracic dysplasia.