[Show abstract][Hide abstract] ABSTRACT: 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.
Breast Cancer Research and Treatment 11/2011; 133(3):969-77. · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Annales de biologie clinique 04/2011; 69(2):167-73. · 0.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 02/2011; 5(1):E4-6. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Cancer 12/2010; 127(11):2669-77. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Breast (Edinburgh, Scotland) 12/2010; 19(6):541-4. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Pathology - Research and Practice 08/2010; 206(8):550-5. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Cancer Science 07/2010; 101(7):1722-30. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Modern Pathology 04/2010; 23(4):522-30. · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Uterine cervix cancer is the second most commonly diagnosed cancer among women worldwide.
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).
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.
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.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(1):235-8. · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
malignant transformation of an epidermal inclusion cyst is rare; this case illustrates the importance of routine histology in excision of epidermal cysts.
North American journal of medical sciences. 01/2010; 2(1):46-7.
[Show abstract][Hide abstract] ABSTRACT: 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.
We describe an unusual case of proliferating bilateral Brenner tumor of the ovary with a highly recurrent low-grade papillary urothelial carcinoma of bladder.
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.
North American journal of medical sciences. 01/2010; 2(1):39-41.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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%).
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.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(3):777-80. · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphoepithelioma - like carcinoma of the bladder is an extremely rare tumour. We discuss through a new case and a review of the literature the pathological pattern and the management of this uncommon entity.
We report the case of a 58 year-old man who presented with a macroscopic hematuria. Transurethral bladder resection was consistent with the diagnostic of a poorly differentiated carcinoma infiltrating the bladder's muscle. A radical cysto-prostatectomy was performed. The pathological examination revealed an EBV negative lymphoepithelioma-like carcinoma of the bladder.
Lymphoepithelioma-like carcinoma of the bladder is a rare bladder cancer that is important to recognize since it has a favourable prognosis.
North American journal of medical sciences. 12/2009; 1(7):375-6.
[Show abstract][Hide abstract] ABSTRACT: Giant cell tumor of soft tissue is a rare primary soft tissue tumor with low malignant potential. It is clinically and pathologically similar to the giant cell tumor of the bone.
We report a case of a 28-year-old man complaining of a painless solitary nodule arising in the spinal muscle of the neck. Computed tomography suggested a neurogenic tumor, but the diagnosis of giant cell tumor was confirmed after detailed pathological examination. The patient remains disease free five months after diagnosis.
It is important to recognize this pathological entity in order to avoid misdiagnosis with other fibrous tumors associated with giant cells.
North American journal of medical sciences. 11/2009; 1(6):319-20.
[Show abstract][Hide abstract] ABSTRACT: Clear cell adenocarcinoma of the urethra is an extremely rare tumour. Its histogenetic derivation remains controversial.
We report a new case of clear cell adenocarcinoma of the proximal urethra in a 56-year-old woman who presented with grossly hematuria. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Treatment consisted of urethrocystectomy with pelvic lymph node dissection. Histologically, the neoplasm consisted of clear cell adenocarcinoma of the urethra.
It appears that female urethral adenocarcinoma has more than one tissue of origin.
North American journal of medical sciences. 11/2009; 1(6):321-3.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
European journal of gastroenterology & hepatology 06/2009; 21(9):1001-7. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sentinel lymph node biopsy (SLNB) demonstrates promising results as an accurate alternative to axillary lymph node dissection in patients with locally advanced breast cancer after neoadjuvant chemotherapy (NAC). However and in the view of the insufficient data on women with inflammatory breast cancer (IBC), SLNB is not recommended in this situation. The current study assessed identification and false-negative rates of SLNB after NAC for patients with IBC.
Between 2006 and 2009, twenty consecutive patients with clinically negative nodes after NAC for IBC (T4d) and who underwent SLNB and axillary lymph node dissection (levels I and II) by the same operator were assessed. Intraoperative Sentinel lymph node biopsy was performed with patent blue dye injections.
The SLN could be identified in 16 of 20 patients (identification rate, 80%), the median of SLN removed per patient was 2 (range 1-3); nine (56%) had positive SLNB, and in 2 of those 9 patients (22%), the SLN was the only positive node with otherwise negative axillary nodes. Two (18%) patients' SLNB were false negative.
The SLN identification and false-negative rates after NAC for IBC were unacceptably high and based on the current findings, SLNB without systematic axillary lymph node dissection is unsuitable in this patient population.
International Journal of Surgery (London, England) 06/2009; 7(3):272-5. · 1.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance.
Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis.
Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of alpha1-antitrypsin precursor (alpha1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated alpha1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of alpha1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of alpha1-AT has been found, thereby suggesting a possible role of this protein in tumor growth.
These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.
Clinica chimica acta; international journal of clinical chemistry 04/2009; 404(2):111-8. · 2.54 Impact Factor