Khaled Rahal

Inflammatory breast cancer in Tunisia: reassessment of incidence and clinicopathological features.

Inflammatory breast cancer (IBC) is a clinical diagnosis characterized by a peculiar geographic distribution in incidence, being particularly common in Tunisia and the region of North Africa. The peculiar aspects of the disease in this region may provide some insights on the biological characteristics of the disease. We updated and revised the data from our single-institution experience using the more stringent diagnostic criteria of the International Union Against Cancer (UICC) based on the tumor-node-metastasis (TNM) classification. The new analysis included 419 newly diagnosed cases of IBC evaluated between 1975 and 1996 that were subdivided into three groups: group A (118 cases classified as T4d in 1990-1996); group B (175 cases reported as Pev 2 or 3 in 1975-81 and restaged as T4d); and group C (126 cases classified Pev 2 or 3 in 1975-81 and restaged as T4b). The frequency of IBC cases classified as T4d in the various series was 5.7% for group A (118/2,073) and 13.3% for group B (175/1,317), while T4b represented 9% for group C (126/1,317). The analysis demonstrated worse 5-year overall survival rates for groups A and B (8.5% and 11.3%, respectively) compared to group C (25.6%). Interestingly, using a more uniform classification criteria, the incidence of IBC was 5% to 7% compared to previous historical reports of up to 50% of newly diagnosed cases of breast cancer in Tunisia.

Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution

Based on two pretreatment evaluations, doubling time (DT) was calculated in 75 cases of invasive breast cancer (BC). The cases studied were more or less equally distributed between three DT groups: fast‐growing tumors (DT < 90 days), intermediate cases (DT between 90 and 180 days), and slow‐growing tumors (DT > 180 days). A correlation was found to exist between DT and patient age and, to an even greater extent, between DT and pathologic prognostic indicators such as histologic grading and nuclear grade. Inflammatory symptoms were not associated with DT, but were closely related to the size of the tumor and regional lymph node involvement. The date of detection of distant metastases depended heavily on the DT of the BC : BC with shorter DT = earlier metastatic spread. The presence of inflammatory signs was also decisive: within each DT category, inflammatory BC metastases were both more frequent and precocious.

Descriptive analysis of molecular subtypes in Tunisian breast cancer

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.

Expression of WISP3 and RhoC genes at mRNA and protein levels in inflammatory and noninflammatory breast cancer in Tunisian patients.

Previous studies have shown the expression WISP3 and RhoC in cell lines of inflammatory breast cancer (IBC). The aim in the current study was to compare the expression of both genes, in biopsy samples collected from Tunisian patients with localized or metastatic breast cancer and patients with IBC. We investigated 127 patients enrolled in Salah Azaiez Institute in Tunis. Using the RT-PCR, we showed the phenotype (WISP3-, RhoC+) is significantly associated with IBC tumors, while the (WISP3+, RhoC-)phenotype is mostly associated to non-IBC tumors. The frequencies of these tumor phenotypes are significantly different between these tumor groups (p = 10(- 7); relative risk or RR = 3.25; confidential interval or CI 95% = 1.90-5.53). Immunohistochemical test revealing the presence of WISP3 and RhoC proteins correlates with the expression in the biopsy of their encoding genes as detected by RT-PCR. In conclusion, it appears that WISP3 and RhoC genes expression status defines a molecular signature of IBC.

Overexpression of FOXM1 Is a Potential Prognostic Marker in Male Breast Cancer

Background: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients remains unknown. We sought to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. Patients and Methods: FOXM1 expression was evaluated in a total of 130 MBC specimens. Results: FOXM1 was overexpressed in 37% of the MBC samples. FOXM1 overexpression was significantly associated with tumor size (p = 0.045), histological grade (p = 0.048), lymph node metastasis (p = 0.012), Ki-67 proliferation index (p = 0.016), and molecular subtypes (p < 0.001). Multivariate analyses indicated that FOXM1 was an independent prognostic factor for overall survival in MBC patients (p < 0.001, hazard ratio = 0.69 (0.43-0.96)). Conclusions: Overexpression of FOXM1 was associated with well-established markers of poor prognosis; thus FOXM1 may represent a potential novel prognostic marker for MBC.

Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer

BACKGROUND In the Tunisian population, as yet a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer. These mutations are located in a few exons of BRCA1/2. The aim of the present study was to search for these mutations in 66 unrelated patients with hereditary breast and/or ovarian cancer in order to assess the interest in such a targeted approach for genetic testing in Tunisia. MATERIALS AND METHODS Blood specimens from the 66 Tunisian patients, with family history of breast and/or ovarian cancer, were collected at the Salah Azaiz Cancer Institute of Tunis. The exons 5, 20 and part of exon 11 of BRCA1 as well as part of exons 10 and 11 of BRCA2 were analyzed by Sanger sequencing. RESULTS 12 patients had deleterious mutations in the BRCA1 or BRCA2 genes (18%), including a novel frame-shift mutation of BRCA1 (c.3751dup; 3780insT). Four distinct BRCA1 mutations were detected eight patients: c.5266dup (5382insC) and c.211dup (330insA) each in three patients, c.3751dup (3870insT) and c.4041_4042del (4160delAG) each in one patient. The four remaining cases all carried the same BRCA2 mutation, c.1310_1313del (1538delAAGA). Besides these deleterious mutations, eight polymorphisms and unclassified variants were detected, one of them being never reported (BRCA1c.3030T>G, p.Pro1010Pro). CONCLUSION In this study, we show that targeting relevant exons in BRCA1 and BRCA2 genes allows detection of a substantial percentage of mutations in the Tunisian population. Therefore such an approach may be of interest in genetic testing of high-risk breast and ovarian cancer families in Tunisia.

MARCKS protein overexpression in inflammatory breast cancer

Background Inflammatory breast cancer (IBC) is the most aggressive form of locally-advanced breast cancer. Identification of new therapeutic targets is crucial. We previously reported MARCKS mRNA overexpression in IBC in the largest transcriptomics study reported to date. Here, we compared MARCKS protein expression in IBC and non-IBC samples, and searched for correlations between protein expression and clinicopathological features. Results Tumor samples showed heterogeneity with respect to MARCKS staining: 18% were scored as MARCKS-positive (stained cells ≥ 1%) and 82% as MARCKS-negative. MARCKS expression was more frequent in IBC (36%) than in non-IBC (11%; p = 1.4E−09), independently from molecular subtypes and other clinicopathological variables. We found a positive correlation between protein and mRNA expression in the 148/502 samples previously analyzed for MARCKS mRNA expression. MARCKS protein expression was associated with other poor-prognosis features in the whole series of samples such as clinical axillary lymph node or metastatic extension, high pathological grade, ER-negativity, PR-negativity, HER2-positivity, and triple-negative and HER2+ statutes. In IBC, MARCKS expression was the sole tested variable associated with poor MFS. Materials and Methods We retrospectively analyzed MARCKS protein expression by immunohistochemistry in 502 tumors, including 133 IBC and 369 non-IBC, from Tunisian and French patients. All samples were pre-therapeutic clinical samples. We searched for correlations between MARCKS expression and clinicopathological features including the IBC versus non-IBC phenotype and metastasis-free survival (MFS). Conclusions MARCKS overexpression might in part explain the poor prognosis of IBC. As an oncogene associated with poor MFS, MARCKS might represent a new potential therapeutic target in IBC.

The “Reverse” Latissimus Dorsi Flap for Large Lower Lumbar Defect

The latissimus dorsi (LD) flap is one of the most common flaps used in plastic surgery based on its dominant thoracodorsal pedicle as well as free tissue transfer. The “distally based” or “reverse” fashion design has been used to repair myelomeningoceles, congenital diaphragmatic agenesis, or thoracolumbar defects. We present a case of a large lumbar defect after cancer resection covered by a combined tegument solution starring the “reverse” LD flap in its muscular version with a cutaneous gluteal flap. This flap is a safe and reliable way to cover large distal lumbar defect.

Triple locations of elastofibroma dorsi: First case report and review

INTRODUCTION Elastofibroma is a rare benign fibroelastic tumor. CASE We report a case of a 44-year-old woman, operated 4 months ago for a left infrascapular desmoid tumor and presented for bilateral mass of the left suprascapular and right infrascapular regions which were surgically resected. The diagnosis of elastofibroma was made and also confirmed for the left infrascapular desmoid tumor. Six months later, she presented an asymptomatic left infrascapular recurrence. Monitoring was continued and the patient is still asymptomatic after 24 months. DISCUSSION We highlight the importance of imaging features understanding in order to avoid misdiagnosis and unnecessary surgical resection.

Results of Second-Look Laparotomy in Advanced Ovarian Cancer: One Single Center Experience

Objective. The goal of the study was to analyse the results of 85 cases of second-look laparotomy (SLL) and explore the influence of this procedure on survival. Patients and Methods. We reviewed retrospectively 85 cases of SLL collected and treated in our institute between 1994 and 2003. Results. Complete pathologic response (CPR) was 25.8%, microscopic disease (Rmicro) was 38.8%, and macroscopic disease (Rmacro) was 35.4%. In patients with negative SLL results, disease recurrence was diagnosed in 41%. The 3- and 5-year overall survival rates for the entire population were 91% and 87%, respectively. The 3- and 5-year disease-free survivals were, respectively, 76.3% and 58.5% in negative SLL versus 55.7% and 16% in positive SLL. The difference between the group of patients with complete response (76%) and the patients with residual microscopic disease (72%) was not significant. The tumoral residuum after initial surgery was the only prognostic factor influencing significantly the disease-free survival. On Cox regression model analysis, only initial tumoral residuum (P = 0.04) and tumoral residuum after SLL (P = 0.02) were independent prognostic factors for survival. Conclusions. The most important advantage of SLL is the early detection of recurrence and thus the early administration of consolidation treatment resulting in a better prognosis.