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Signal transducers and activators of transcription 5a and 6 (STAT5a and STAT6) play a critical role in tumorigenesis of mammary glands. Based on previous studies, the breast cancer is largely dependent on hormone receptors. Consequently, it is very interesting to decipher the relationship between the STAT5a and STAT6 expression and the molecular distribution of estrogen receptors (ERs) and progesterone receptors (PRs) in mammary tumors.Our study analyzed the expression of STAT5a and STAT6, ERα, ERβ and PR in 40 breast tumor tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the Ki-67 and HER2 status were detected using immunohistochemistry.STAT5a and STAT6 were retained in the majority of the cases studied. Increasing of STAT5a and STAT6 is significantly associated with ERs and PR. The coexpression of both STAT5a and STAT6 with ERs and PR is associated with high tumor grades. Moreover, the coexpression of STAT5a and STAT6 with ERα and PR is associated with a high proliferation index. In addition, (STAT6 + ERβ+) and (STAT6 + PR+) breast cancer subgroups are associated with lymph node infiltration (P = 0.001 and P = 0.03, respectively).Our study results provide an interaction between STAT5a and STAT6 with ERs and PR inducing cell proliferation. Coexpression of STAT5a and STAT6 with ERs and PR can predict sensibility to hormonal therapy.

DNA hypomethylation of long interspersed repetitive DNA retrotransposon (LINE-1) and Alu repeats elements of short interspersed elements family (SINEs) is an early event in carcinogenesis that causes transcriptional activation and leads to chromosomal instability. In the current study, DNA methylation levels of LINE-1 and Alu repeats were analyzed in tumoral tissues of invasive breast cancer in a Tunisian cohort and its association with the clinicopathological features of patients was defined. DNA methylation of LINE-1 and Alu repeats were analyzed using pyrosequencing in 61 invasive breast cancers. Median values observed for DNA methylation of LINE-1 and Alu repeats were considered as the cut-off (59.81 and 18.49%, respectively). The results of the current study demonstrated a positive correlation between DNA methylation levels of LINE-1 and Alu repeats (rho=0.284; P

Clinical implications of single nucleotide polymorphisms (SNPs) in breast cancer have been explored to determine the impact of SNP in modulating the pathogenesis of breast cancer. This study aimed to evaluate the association between HER2 (rs2517956) and (IL-6) (rs1800795 and rs2069837) and clinicopathological characteristics in HER2-positive and HER2-negative breast cancer in Tunisian women. A retrospective cohort study included 273 patients. Genomic DNA was extracted from peripheral blood samples, and genotyping of selected SNP was performed by PCR–RFLP assays. Statistical analysis was then carried out to assess genotypic frequencies and genetic association in relation to breast cancer subtypes. SHEsis software was applied to IL-6 haplotypic structure analysis. The distribution of genotype frequencies of rs2517956, rs1800795 and rs2069837 showed no statistically difference between HER2-positive and HER2-negative breast cancer. HER2 (rs2517956) was associated with tumor size (p = 0.01) and age at diagnosis (p = 0.02) in HER2-negative breast cancers, but no significant association was observed in HER2-positive breast cancer. For IL-6 gene, none of the clinicopathological parameters were associated with rs1800795 and rs2069837 in both breast cancer subtypes (p > 0.05). SHEsis analysis revealed a high linkage disequilibrium between rs1800795 and rs2069837; differences in the distribution of IL-6 two loci haplotypes were statistically negative between HER2-positive and HER2-negative breast cancer (p = 0.20) which confirmed no association with HER2 overexpression. This study demonstrates that rs2517956 is associated with clinicopathological characteristics in HER2-negative breast cancer, which could have a differential prognostic role compared to HER2-positive breast cancer.

Background Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. In female breast cancer, PD-L1 expression has been correlated with poor clinical outcome. However, whether PD-L1 has any indication for prognosis in male breast cancer (MBC) patients remains unknown. The purpose of this study was to examine the expression levels of PD-L1 in MBC and to identify the relationship between PD-L1 expression and patient survival. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. PD-L1 expression was evaluated by immunohistochemistry (IHC) using CD274 antibody. Specimens were scored as IHC low or high, when < 5% or ≥ 5% of cells were PD-L1 positive, respectively. The association between expression of PD-L1 and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results Median follow up was 12.5 months [range 1-132 months]. High expression of PD-L1 was observed in 64.5% of MBC samples (71/110). PD-L1 expression was significantly associated with advanced clinical stage (p=0.012), higher histological grade (p=0.014), higher Ki67 expression (p=0.023) and hormone-receptor negative status (p=0.024). Patients with high PD-L1 expression had significantly shorter overall survival (OS) than patients with low expression (p=0.002, hazard ratio (HR) =5 [2.624–10.642]). Multivariate analysis identified PD-L1 as an independent prognostic factor for OS (p Conclusion Our results indicate that high PD-L1 expression may be a prognostic indicator for reduced OS. Thus, PD-L1 expression is a promising novel biomarker with prognostic significance in MBC and may suggest a potential therapeutic target of anti-PD-L1 antibody therapy in MBC patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Chiba D, Bouzaiene H, Ben Hassouna J, Boussen H, Rahal K, Gamoudi A. Prognostic value of PD-L1 expression in male breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-05.

Background Several studies have demonstrated that the presence and the amount of tumor-infiltrating lymphocytes (TILs) are a potential biomarker of prognostic significance in some solid tumors. Data suggests that high levels of TILs are associated with favorable prognosis. However, whether TILs have any indication for prognosis in male breast cancer (MBC) patients remains unknown. In this study, we investigated the relationship between the expression and degree of CD8+ TILs, CD4+ TILs, and TILs and evaluated the prognostic value of these three factors in MBC. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. Stromal (str) CD8+ and CD4+ TILs were evaluated immunohistochemically. Two pathologists independently evaluated TILs levels using H&E stained slides following 2014 International TILs Working Group guidelines. Kaplan Meier and univariate and multivariate Cox regression analysis were applied to determine the association of CD8+ TILs, CD4+ TILs and TILs with clinicopathological features and overall survival (OS). Results The median for presence of str-CD8+TILs was 7% (0%-40%), str-CD4+TILs was 2% (0%-20%) and str-TILs was 10% (1%-40%). Only 12% of MBC patients had high str-CD8+TILs and 11% had high str-CD4+TILs. Fifty three percent had low str-TILs and 47% had moderate str-TILs. No lymphocyte predominant breast cancer was identified. Regarding intrinsic molecular subtypes, TNBC subtype and HER2 enriched tumors compared with Hormone receptor positive tumors had higher median levels of str-CD8+TILs, str-CD4+ TILs and str-TILs at diagnosis. However, increased level of str-CD8+ TILs, str-CD4+TILs and str-TILs weren't associated with improved OS in IHC subtypes (p=0.597, p=0.498 and p=0.456 respectively). On univariate analysis, higher levels of str-CD8+TILs, str-CD4+ TILs and str-TILs were associated with better OS (p=0.035, p=0.043 and p=0.040 respectively). Multivariate analysis identified str-CD8+ TILs and str-TILs as independent prognostic factors for OS ([HR= 0.851 (0.706-0.997), p=0.000] and [HR= 0.69 (0.43-0.96), p=0.045] respectively) but not str-CD4+ TILs (p=0.276). A high level of str-TILs was correlated with high str-CD8+ (p = 0.025). Conclusion The level of TILs in male breast cancer is low, suggesting prominent immune regulation/suppression in this disease. Str-CD8+ T cells and str-TILs represent potential prognostic markers in male breast cancer patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Ghozzi R, Bouzaiene H, Hdiden M, Ben Hassouna J, Makhlouf R, El Benna F, Boussen H, Rahal K, Gamoudi A. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs), CD4+ TILs and TILs in male breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-15-01.

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.

BACKGROUND Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial. OBJECTIVE Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) in MBC and to investigate its prognostic value. MATERIALS AND METHODS MARCKS protein expression in tumor and stromal cells was analyzed by immunohistochemistry (IHC) in a retrospective series of 96 pre-chemotherapy MBC samples and 80 normal breast samples, from Tunisian patients treated at Salah Azaiez Institute. Correlations were searched between MARCKS expression and clinicopathological features including overall survival (OS). RESULTS MARCKS was overexpressed in epithelial tumor cells in 66% of the MBC samples versus 26% of normal samples (p= 1.40 × 10-7). Such positive MARCKS expression in epithelial tumor cells was associated with positive HER2 status (p= 4.0 × 10-3). It was associated with shorter OS in uni-and multivariate analysis. By contrast, stromal IHC MARCKS expression was correlated only with tumor grade. CONCLUSION MARCKS tumor cell overexpression might in part explain the aggressiveness and the poor prognosis of MBC. MARCKS can represent a potential therapeutic target for MBC.

Objectives To compare the histopathological features and survival of triple-negative breast carcinomas (TBNC) in younger and older women. Methods We documented 300 patients with TBNC between 2009 and 2013. The histopathological and clinical features of women who were 35 years old or younger (N=) were compared to those of women who were 60 years old and older (N=). Patients were administered adjuvant or neoadjuvant chemotherapy, and adjuvant radiotherapy. Results We diagnosed and treated a total of 300 patients with TNBC. The median follow-up was 38 months. The median age of the younger patients was 32 years ( range:19–36) and of older patients 67 years ( range:60–84). The tumor size in young patients was larger than in older patients (p=0.001). More comorbid diseases were observed in older patients than in younger ones (p=0.001). There was no difference in the histological grades, lymphovascular invasion, stage and nodal involvement between the two groups. Local/distant metastases were found in 11 (40.7%) patients in the young patient group and in 16 (59.3%) in old patient group (p=0.704). Three (5.4%) patients died from each group. No significant difference in terms of disease-free survival (DFS) and overall survival (OS) (p=0.914, p=0.939, respectively) was noticed. Conclusions This study showed that older and younger patients with TNBC had similar survival with neoadjuvant and adjuvant chemotherapy and adjuvant radiotherapy, which may be due to similar histopathologic features and intrinsic tumors’ characteristics.

Objectives We studied characteristics of patients with non metastatic TNBC and assessed survival outcomes and prognostic factors. Methods We searched our Institute of Cancer registry database and identified patients with TNBC without distant metastatic disease. We retrieved demographic, tumour characteristic and treatment information. Locoregional recurrence-free survival, breast cancer-specific survival (BSS), metastasis-free survival (MRFS) and overall survival were determined.Predefined univariate and multivariate analyses were carried out investigating the association of survival outcomes with treatment and tumour characteristics. Results In total, 275 patients were identified, with a median follow-up of 3.5 years. The median age was 55 years. Thirty-eight per cent were node positive and 79% were grade III. Mastectomy was carried out in 53%, adjuvant radiation delivered in 66% and chemotherapy in 69%. The significant predictive factors for overall survival, BSS and MRFS were radiotherapy, chemotherapy and neoadjuvant chemotherapy. The significant prognostic indicators were lymphovascular invasion, nodal status and tumour size. On KaplaneMeier analysis, the 5 year overall survival was 72%. The median time to death for those who died was 3.55 years with 92% of deaths within 5 years. Seventy-four per cent of patients had distant metastasis as a first recurrence and isolated local recurrences occurred in only 4.5%. Metastatic disease occurred in lung (55.9%) and was in multiple sites in 51%. Conclusions Althought standard therapies are positively associated with survival outcomes particularly in the setting of recurrent disease the prognosis remains poor. Increased research into more effective systemic agents and the most effective timing of delivery of these may result in improved outcomes.

Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition.

e13609Background: Breast cancer, the first malignant disease in women, remains a rare disease in men. Given the rarity of this disease, the only way to study its characteristics is the retrospectiv...

Gigantomastia is a rare mastopathy of unknown cause. Due to mechanical and psychological complications related to excessive breast weights and volume, effective surgical treatment is required. Most cases of gigantomastia in the literature are associated with pregnancy or puberty and very rare cases of spontaneous gigantomastia have been reported We report a 38 years old woman with an idiopathic gigantomastia treated successfully with Thorek technique.

Ganglioneuroma is a rare benign tumor. It is the most mature of neurogenic tumors. We report a case of a pelvic ganglioneuroma diagnosed in 24-year-old pregnant woman who presented with an urinary infection. Echographic examination suggested an ovarian mass. At surgical operation, the tumor was close to the sacrum. A total resection of the tumor was performed. Pathological examination proved it as a ganglioneuroma. Sixteen months later, the patient is free from disease.

Endometrial adenofibroma is an uncommon mullerian mixed tumor composed of benign epithelial and mesenchymal components. This tumor must be distinguished from other malignant lesions of the uterus, particularly adenosarcoma. The authors report three cases of endometrial adenofibroma and discuss their clinical and histopathologic features. The tumors were diagnosed in patients 31, 55 and 63 years of age. In all three cases polypoid lesions of 13, 2 and 5 cm, respectively, were found in the uterine cavity. A polypectomy was performed in two cases; one patient underwent hysterectomy. Follow-up was available for two patients who are today alive and well.

Epithelioid hemangioma of bone is a rare benign vascular lesion. Since its first description by Rosai in 1979 about thirty cases have been reported. We report two new cases diagnosed in patients aged 21 and 7 years. Both patients had multiple lesions on the legs. Bone pain was the main symptom. Routine laboratories studies were unremarkable. Bon radiographs showed an expansive process of the bone. Histological and immunochemical features were typical of epithelioid hemangioma of the bone. Treatment consisted in above knee amputation for the first patient and therapeutic abstention for the second. Both patients are alive without progressive local disease or metastasis.