Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions.

BACKGROUND: Little is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women. METHODS: Cross-sectional study was performed on 494 Tunisian women visiting Women's Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene. RESULTS: The overall HPV prevalence was 34% (95% CI: 30-38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76-92%) and 24.5% (95% CI: 20-29%) respectively. The distribution of HPV prevalence according to women's age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37-67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22-45%) among women with SIL and 9.2% (95% CI: 6-12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0-5%) among women with SIL and 0.3% (95% CI: 0-1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76-95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64-99%, and 88%, 95% CI: 77-100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1-36% and 6%, 95% CI: 2-14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL. CONCLUSION: HPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

[The therapeutic contribution of proteomic approaches in cancers]. / L'apport thérapeutique des approches protéomiques dans les cancers.

Up to now, there are no protein tumor markers with a specificity and sensitivity sufficient to have a utility in prognosis and early diagnosis of cancer. Recent advances in proteomics approaches have led to the identification of novel tumor markers of cancer that may have a utility in screening strategies and treatment. The purpose of the current review is to describe the major advances in cancer proteomics, especially those related to the study of serum biomarkers, immune-related responses (autoantibodies) and alterations in cellular proteins.

[Ovary tumor in chronic myeloid leukaemia. Case report]. / Tumeur ovarienne et diagnostic de leucémie myéloïde chronique. A propos d'un cas.

Granulocytic sarcoma or chloroma is a neoplasia consisting of myeloid precursors in an extramedullary site. Its appearance in chronic myeloid leukaemia is unusual. We report a case of ovary tumor associated with chronic myeloid leukaemia in chronic phase.

Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma.

Glutathione S-transferase Theta1 and Mu1 (GSTT1 and GSTM1) are involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. Conversely, they contribute to tumour cell survival by detoxification of numerous products induced by cancer therapy. The authors designed a large study to investigate the susceptibility and prognostic implications of the GSTT1 and GSTM1 gene deletions in breast carcinoma. The authors used the polymerase chain reaction to characterise the variation of the GSTT1 and GSTM1 genes in 309 unrelated Tunisian patients with breast carcinoma and 242 healthy control subjects. Associations of the clinic-pathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) were assessed using univariate and multivariate analyses. A significant association was found between gene deletion of GSTT1 and the risk of early onset of breast carcinoma (OR=1.60, P=0.02). The lack of GSTT1 gene deletion was significantly associated with poor clinical response to chemotherapy (OR=2.29, P=0.03). This association was significantly higher in patients with axillary's lymph node-negative breast carcinoma (OR=12.60, P=0.005). The null-GSTT1 genotype showed a significant association with increased DFS in this selected population of patients. This association was even higher in patients carrying both null-GSTT1 and -GSTM1 genotypes. The gene deletion of GSTs may predict not only the early onset of breast carcinoma but also the clinical response to chemotherapy and the recurrence-free survival for patients with lymph node-negative breast carcinoma.

Cervical human papillomavirus infection in Tunisian women.

BACKGROUND: It is well established that certain types of human papillomavirus (HPV) are the sexually transmitted agents etiologically linked to cervical cancer. Sexual habits have been shown to be a major determining factor for HPV infection. A large study was carried out to investigate the prevalence and risk factors associated with cervical infection with HPV in Tunisian women. MATERIALS AND METHODS: PCR and restriction enzyme digestion were used to characterize HPV cervical infection in 106 Tunisian married women and 51 legal prostitutes. Epidemiological data were collected and correlated with HPV molecular genotyping. RESULTS: There was a higher relative frequency of HPV-DNA in prostitutes (39%) than in married women (14%) (p = 0.001). Molecular analyses of HPV types showed the most prevalent type in prostitutes to be HPV-16, a high-risk oncogenic type. In married women, the most prevalent type was HPV-6 which is associated with a low risk for cervical cancer. HPV-DNA detection was markedly increased in young adult women and in those having recent sexual experience. CONCLUSION: Cervical HPV infection in Tunisia is less frequent than in other African countries, but far from uncommon. The decrease of HPV prevalence in older women, regardless of their sexual behavior, may result from an efficient immune response acquired with age.

Functional evaluation of plasmin formation in primary breast cancer.

PURPOSE: Plasmin generation is controlled by the plasminogen activators (PA)/plasmin system, which comprises proteases (urokinase-type PA [uPA] and tissue-type PA [tPA]) and antiproteases (PA inhibitors, PAI-1 and PAI-2). The tumoral content of uPA and PAI-1 has been shown to carry prognostic value in breast cancer; however, because most assays used so far have relied on immunometric determinations, we have explored the enzymatic activities governing plasmin formation in breast cancer specimens. PATIENTS AND METHODS: We applied semiquantitative histochemical zymography to 201 primary breast cancer tissue sections. Enzymatic activities were correlated with histopathologic parameters and clinical outcome. The median follow-up was 91 months. RESULTS: A wide range of PA-mediated catalytic activities was detected. The overall survival was significantly worse for patients with tumors showing tPA in the lowest quartile of activity (P =.003). The 5-year overall survival of patients with tPA activity in the lowest quartile was 58% compared with 81% for patients with tPA value in the other three quartiles. Tumor size, axillary lymph node metastasis, histologic grade, lymphovascular infiltration, TP53 mutation, and tPA activity were all major risk factors in univariate analysis. tPA activity was an independent prognostic factor in a multivariate Cox regression model, both in the whole population (relative risk = 0.5, 95% confidence interval, 0.3 to 0.9; P =.02) and in the node-negative subgroup (relative risk = 0.2, 95% confidence interval, 0.08 to 0.6; P =.004). CONCLUSION: By using a zymographic assay performed directly on primary tumor tissue sections, we demonstrate that reduced tPA-mediated plasmin production is an independent adverse prognostic factor in breast cancer.

Genetic variation in the tumor necrosis factor-alpha promoter region and in the stress protein hsp70-2: susceptibility and prognostic implications in breast carcinoma.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and stress proteins (heat shock proteins) are determining factors in the immune response to tumor cells. The authors designated a large study to investigate the susceptibility and prognostic implications of the genetic variation in TNF-alpha and hsp70-2 in breast carcinoma. METHODS: The authors used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the hsp70-2 gene in 243 unrelated Tunisian patients with breast carcinoma and 174 healthy control subjects. Associations of the clinicopathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival and the disease free survival (DFS) were assessed using univariate and multivariate analyses. RESULTS: A highly significant association was found between TNF2 homozygous genotype and breast carcinoma (relative risk [RR], 4.44; P = 0.006). A high relative risk of breast carcinoma was found to be associated with one hsp70-2 homozygous genotype (P2/P2; RR, 7.12; P = 0.0001). The TNF2 homozygous genotype showed a significant association with reduced DFS and/or overall survival by univariate test. Conversely, P2-hsp70-2 homozygous genotype associated with increased overall survival but not with DFS. Multivariate analysis retained significance for TNF2 homozygous genotype as an independent prognostic indicator for both DFS (RR, 2.75; P = 0.01) and overall survival (RR, 4.08; P = 0.01). CONCLUSIONS: Genetic variation in TNF-alpha and hsp70-2 may represent not only markers for the increased risk of breast carcinoma but also may predict the clinical outcome.

A case of endometrioid carcinoma of the fallopian tube mimicking an adnexal tumor of probable Wolffian origin.

We report a very uncommon case of endometrioid adenocarcinoma of the fallopian tube that mimicked, based on histology, a female adnexal tumor of probable Wolffian origin (FATPWO). We present our microscopic and immunohistochemical findings, and a review of the literature concerning these two entities. The differential diagnosis can be of great consequence, owing to the very different prognoses of the two tumors, and is based mainly on macroscopic appearance and immunohistochemical profile: epithelial membrane antigen (EMA) and CA125, generally lacking in FATPWO, are expressed in endometrioid adenocarcinoma, thus indicating the müllerian origin of this tumor.

Wilms' tumor in the adult--report of a case and review of the literature.

Wilms' tumor is rare in adults. Its histology, grading and staging are identical to those in children. Investigators agree on a combined modality approach in the treatment of adult Wilms' tumor (AWT), but differ on how aggressive it should be. Some advocate adopting the current pediatric protocols which take into account tumor stage and grade. Others recommend using advanced disease regimens for all stages and grades. We report on an 18 year-old male with stage IV favorable histology Wilms' tumor. The patient underwent radical nephrectomy and received postoperative radiotherapy with intensive four-drug chemotherapy. He had one relapse after 12 months which was successfully treated with chemotherapy and radiotherapy. He remains in remission without relapses 36 months after the initial diagnosis. The genetics of Wilms' tumor has been well studied in children but is practically unknown in adults; karyotype and molecular genetic studies in this case were normal.

[Detection and molecular typing of human papillomaviruses: prevalence of cervical infection in the Tunisian central region]. / Detection et typage moleculaire des Papillomavirus Humains: prevalence de l'infection cervicale dans la region du centre Tunisien.

There are compelling molecular and epidemiological data which indicate that infection with certain genital human papillomaviruses (HPVs), such as HPV 16 and HPV 18, has a critical role in initial changes that lead to cervical and probably other anogenital cancers. These observations prompted us to investigate the prevalence of cervical infection with genital human papillomaviruses in Tunisia. We used the polymerase chain reaction (PCR) to detect and type HPV DNA. The prevalence of HPV infection in a population of 106 Tunisian women recruited at the Offices Nationaux de la Famille et de Population (ONFP) was 13.6%. Molecular HPV typing indicated a high prevalence of HPV at high oncogenic risk; Our results indicate that the infection with genital human papillomaviruses is frequent in the Tunisian population.

Well differentiated cerebellar tissue within a mature cystic teratoma.

We describe the case of a 27 year-old woman presenting with acute abdominal pain due to torsion of a right ovarian cyst. Histopathological examination of the excised lesion revealed a mature cystic ovarian teratoma consisting primarily of a highly organized cerebellar component, an exceedingly rare finding. The possibility of a malignant neuroepithelial tumor arising from immature precursor cells within this neural tissue justifies complete excision of such lesions.

Apparent lack of prognostic value of MIB-1 index in anal carcinomas treated by radiotherapy.

This study was conducted to investigate the influence of Mib-1 index on outcome in 55 patients with T1-4 anal carcinomas treated radically by radiotherapy (RT) alone (24) or by concomitant chemo-radiotherapy (31). Median follow-up for surviving patients was 94 months (range 17-179 months). Tissue materials were obtained from pretreatment biopsies. A modified immunoperoxidase technique consisting of microwave heating of routinely processed material was employed using the Mib-1 antibody (Immunotech, 1:50). The median Mib-1 index for all patients was 53% (range 18-96%). Subgroups of patients with high vs low Mib-1 indices (separated by the median value) had statistically similar outcomes regarding 5-year overall survival (64% vs 65% P = 0.7), locoregional control (77% vs 69%, P = 0.5) and disease-free survival (73% vs 66%, P = 0.5). Moreover, no significant association was found between mean Mib-1 indices and various clinicopathological parameters studied (age, sex, circumferential tumour extent, T-stage, N-stage and histological type). In conclusion, Mib-1 index failed to predict the outcome of patients with anal carcinomas treated conservatively by radiotherapy with or without chemotherapy. It is noteworthy that the median Mib-1 index observed in anal carcinomas in this study was among the highest yet reported for cancers of epithelial origin.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase immunohistochemical expression in lymphoid tissue and lymphoid malignancies.

The catabolic enzyme thymidine phosphorylase (TP) plays a crucial role in nucleic acid metabolism by regulating the availability of thymidine. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that was recently shown to be TP. The angiogenic properties of PD-ECGF/TP are attributable to a reduction of thymidine levels that results in a promotion of endothelial cell proliferation. Early studies showed a higher concentration of TP in macrophages than in parenchymal cells and in neoplastic than in nonneoplastic tissues. We examined the immunohistochemical expression of PD-ECGF/TP in reactive lymphoid tissues (lymph node and tonsil), as well as in a series of 20 cases of Hodgkin's disease and 31 cases of non-Hodgkin's lymphomas. Macrophages, sinus lining cells, and cells with dendritic morphology, of both follicular dendritic and interdigitating reticular cell type, presented a prominent nuclear and cytoplasmic positivity in reactive lymphoid tissue and in malignant lymphomas. Small lymphocytes and the neoplastic population were always negative, whereas endothelial staining was variable and showed no correlation to the type or grade of the lymphomas. In Hodgkin's disease (with the exception of the nodular lymphocyte predominance type) and some cases of high-grade non-Hodgkin's lymphomas, the positive dendritic cells formed a dense meshwork closely surrounding the neoplastic population. Our results suggest that the reported upregulation of PD-ECGF/TP activity in lymphoid malignancies is attributable to the nonneoplastic population, especially to cells of dendritic morphology.

Polymorphism in the tumor necrosis factor-alpha promotor region and in the heat shock protein 70 genes associated with malignant tumors.

BACKGROUND: Tumor necrosis factors (TNFs) and heat shock protein 70 (hsp70) are determining factors in immunologic mechanisms to tumor cells. The authors designed a case-controlled study to investigate the potential association of the polymorphisms of TNF-alpha and of hsp70-2 and hsp70-hom genes with malignant tumors. METHODS: The authors used an allele specific polymerase chain reaction to characterize the variation of the TNF-alpha promotor region in 124 unrelated Tunisian patients with malignant tumors (non-Hodgkin's lymphoma, breast carcinoma, and other tumors) and 106 healthy control subjects. Using polymerase chain reaction and restriction enzyme digestion, polymorphic analysis of hsp70-2 and hsp70-hom genes was performed in patients with non-Hodgkin's lymphoma, in those with breast carcinoma, and in control subjects. RESULTS: Analysis of TNF-alpha polymorphism in patients with malignant tumors and in control subjects demonstrated a high relative frequency of the TNF2 allele in the cancer patients. The relative risk (RR) of lymphoma was especially high in association with TNF1/TNF2 heterozygotes (RR = 6.7; P < or = 0.0001). Polymorphism analysis of the hsp70-2 and hsp70-hom genes in patients with lymphoma and in those with breast carcinoma revealed that these patients had highly significant differences in the genotypic distribution of these biallelic loci compared with the control subjects. Homozygosity for one hsp70-2 allele was significantly associated with lymphoma (RR = 18.2; P < or = 0.0001) and with breast carcinoma (RR = 16.3; P < or = 0.001). CONCLUSIONS: Tunisian persons carrying the TNF2 allele may have an increased risk of cancer. In this study, non-Hodgkin's lymphoma and breast carcinoma were significantly associated with polymorphism in hsp70 genes.

Cytologic diagnosis of isolated pancreatic alveolar hydatid disease with immunologic and PCR analyses. A case report.

BACKGROUND: Alveolar hydatid disease (AHD) is a rare and severe parasitic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis. AHD mainly involves the liver, and although it may extend progressively to the pancreas, isolated pancreatic localization has not been reported previously. CASE: A 68-year-old white female presented with a multicystic mass in the pancreas. Fine needle aspiration showed some protoscolices, free hooklets and fragments of laminated layer, which are pathognomonic features of echinococcosis. Serologic analyses by an enzyme-linked immunosorbent assay using Em2plus antigen showed high antibody reactivity of the patient's serum, which is indicative of an infection with E multilocularis. Diagnosis was finally confirmed by molecular and immunologic analyses of the cytologic material by polymerase chain reaction and direct immunofluorescence. CONCLUSION: This case illustrates the value of cytology in the identification of echinococcosis, particularly when it involves extrahepatic sites, where the risk of misdiagnosis may be related to its extremely rare occurrence. Precise parasitologic tying of E multilocularis in endemic areas is important.

Adenoid cystic carcinoma of the breast: utility of immunocytochemical study with collagen IV on fine-needle aspiration.

A case of adenoid cystic carcinoma (ACC) of the breast in a 71-year-old woman is reported. This neoplasm accounts for about 0.1% of all breast cancers. The mammography showed a well-delineated mass without calcifications. Cytologic examination of percutaneous fine-needle aspiration (FNA) material gave the diagnostic of ACC, which was confirmed by histologic examination. This report emphasizes the utility of immunocytochemical study with collagen IV antibody on FNA material of this uncommon tumor.

Polymorphism in transporter antigen peptides gene (TAP1) associated with atopy in Tunisians.

BACKGROUND: Transporter antigen peptide 1 (TAP1) and TAP2 gene products from a transporter molecule involved in antigen presentation. Polymorphic residues have been described in both genes and could have functional consequences in the immune response. OBJECTIVE: We designed a case-control study to investigate the potential association of polymorphism of the TAP1 gene with atopy. METHODS: We used the amplification refractory mutation system polymerase chain reaction to characterize TAP1 gene polymorphism in 84 unrelated Tunisian patients with atopy and 81 healthy control subjects. RESULTS: Analysis of TAP1 polymorphism in Tunisian patients with atopy and in unaffected control subjects demonstrates a high relative risk (RR) of atopy in carriers of a codon (d) corresponding to a glycine at position 637 of the TAP1-B and TAP1-D alleles. The relative risk of allergic asthma is markedly higher in homozygotes (d/d) (RR = 22; p < or = 0.0001). The TAP1-D allele, not observed in European populations, has a frequency of 5% in the Tunisian control subject group. 4 major increase of the frequency (f) of the D allele is observed in patients with allergic asthma (f = 35%) and in those with allergic rhinitis (f = 22%), indicating a high relative risk of allergic asthma (RR = 10.2; p < 0.0001) and of allergic rhinitis (RR = 5.4; p < or = 0.005) in individuals carrying this allele. DD homozygotes were found only among patients with allergic asthma (23% of patients with asthma). Further evidence of the strong association between TAP1 polymorphism and atopy was provided by the finding that atopy is transmitted by inheritance of the glycine-637 marker. CONCLUSIONS: Tunisian persons carrying the glycine-637 of the TAP1 protein may have an increased risk of atopy. Specific association was found between the homozygous TAP1 D/D genotype and allergic asthma.

Ovarian metastatic melanoma. A diagnostic pitfall in histopathologic examination.

Malignant melanoma metastasis to the ovary is exceptional. This observation relates the case of a 33 year-old woman who presented with a voluminous unilateral, histologically poorly differentiated, ovarian mass, and discusses the differential diagnosis. Immunohistochemical studies demonstrated strong positivity for S-100 protein, HMB-45 and vimentin. We emphasize the unpredictable clinical and biologic behavior of malignant melanomas and the necessity to perform immunohistochemical study by S-100 protein and HMB-45 in a poorly differentiated metastasis to the ovary, histologically compatible with malignant melanoma; even in the absence of intracytoplasmic pigment and clinical antecedent of cutaneous malignant melanoma.

Metastasizing placental site trophoblastic tumor: immunohistochemical and DNA analysis. 2 case reports and a review of the literature.

Placental-site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia. The clinical behaviour of PSTT is usually benign, but sometimes it can be highly malignant with late recurrence and metastasis. We describe two cases of PSTT with pulmonary metastasis in patients aged 35 and 29 years respectively. The mitotic rate was elevated to 9 and 13 mitotic figures per 10 high-power fields respectively. Immunohistochemical staining showed a predominance of human placental lactogen (hPL) positive cells when compared with human chorionic gonadotropin (hCG) reactive cells in one case, and a reverse pattern in the other one. DNA measurement in one case showed an aneuploid tumor with a tetraploid DNA peak. The clinical behaviour of PSTT remains unpredictable, and there are no reliable means of predicting clinical outcome.