FOXP3+/CD68+ ratio within the tumor microenvironment may serve as a potential prognostic factor in classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (CHL) is characterized by extensive inflammatory immune cells, which predict the disease prognosis. Therefore, this study aimed to explore the significance of different tumor-infiltrated immune cells and subpopulation ratios observed in the tumor microenvironment of CHL, particularly relating to the disease's prognosis-focusing on overall survival (OS) and event-free survival (EFS). Utilizing immunohistochemistry, the quantification and exploration of selected immune cells' subsets, including CD3+, CD4+, CD8+, FOXP3+, CD20+, and CD68+ were conducted on 102 histological samples with primary CHL. Eosinophils were pathologically assessed. Besides, we determined the ratios between different tumor-infiltrated immune cells for each patient. Kaplan-Meier method and Cox regression modeling were used for survival analysis. We demonstrated that among all ratios and immune cells individually, only a higher FOXP3+/CD68+ ratio (≥1.36 cutoff) displayed a tendency towards a favorable OS (p = 0.057, HR = 0.43 [0.18-1.02]) and EFS (p = 0.067, HR = 0.44 [0.18-1.06]) using Cox regression modeling. Moreover, the Kaplan-Meier method showed an association of a higher FOXP3+/CD68+ ratio with a longer 5-years OS (p = 0.037) and a tendency to a better EFS (p = 0.051); however, neither the combined FOXP3+ and CD68+ nor FOXP3+ or CD68+ separately was correlated to the CHL survival. Together, these results demonstrated that the FOXP3+/CD68+ ratio could predict the outcomes of CHL, providing more informative significance than FOXP3+ and CD68+ combined or FOXP3+ and CD68+ individually and might be a potential indicator of risk stratification, which has an important value for guiding the clinical treatment.

Association of ZEB1 and Vimentin with poor prognosis in metaplastic breast cancer.

Zinc finger E-box binding homeobox factor 1 (ZEB1) is a transcription factor involved in the epithelial to mesenchymal transition (EMT) process of metaplastic breast cancer (MBC). This study aimed to assess the expression of ZEB1 in MBC and explore its association with clinicopathological factors and prognosis. We analyzed the immunohistochemical expression of ZEB1 in 50 MBC tissue samples. ZEB1 was overexpressed in 36% (18/50) of cases. ZEB1 overexpression was significantly correlated to fibromatosis-like and spindle cell sarcoma subtypes (P < 0.001) and tended to be correlated to metastatic status (P = 0.069). Using the Kaplan-Meier method, ZEB1 expression was significantly associated with poor 5-years overall survival (OS) (P = 0.001) and relapse-free survival (RFS) (P = 0.0001). The multivariate Cox regression analysis showed that ZEB1 positive remained a significantly independent adverse prognostic factor for RFS and OS (HR = 4.9 [2.14-11.53]; P < 0.0001) and (HR = 4 [1.05-15.18]; P = 0.042), while Vimentin was an independent poor prognostic factor only for RFS (HR = 5.69 [1.79-18.11], P = 0.003). Our results indicated that ZEB1 and Vimentin overexpression might serve as adverse prognostic factors and potential therapeutic targets for MBC patients.

Tumor DNA hypomethylation of LINE-1 is associated with low tumor grade of breast cancer in Tunisian patients.

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<0.03). DNA hypomethylation of LINE-1 was also indicated to be associated with low grade (P=0.023). To the best of our knowledge, the current study is the first study regarding DNA methylation of LINE-1 and Alu repeats element in breast cancer of the Tunisian population. The results of the current study suggest that, since hypomethylation of LINE-1 is associated with low grade, it could be used as a biomarker for prognosis for patients with breast cancer.

Prostate adenorcarcinoma revealed by gingival metastasis: An uncommon presentation.

Prostate cancer is the second most frequent among men. Bones and lymph nodes are the most common sites of metastases in advanced prostate cancer. Oral cavity metastases are rare. We report a case of 65-year-old man with a prostate adenocarcinoma revealed by gingival metastasis. We analyze through this observation the clinical, morphological and therapeutic characteristics of this neoplasia.

The Prognostic Significance of IGF-1R and the Predictive Risk Value of Circulating IGF-1 in Tunisian Patients with Laryngeal Carcinoma.

The aim was to evaluate the clinical impact of IGF-1/IGF-1R in Tunisian laryngeal carcinoma. A high IGF-1R immunohistochemical expression was found in our series (81.43%). A tendency toward an association between IGF-1R expression and lymph node metastasis was found (p = 0.068). Patients with positive IGF-1R expression showed a short disease free survival (p = 0.053) and a high recurrence rate. Furthermore, circulating IGF-1 levels sera, detected by ELISA, were higher among patients compared to controls (p < 0.001). IGF-1R might have a prognostic significance and could be a factor of tumor recurrence. However, high levels of IGF-1 increase the risk of developing of LSCC disease.

Pure Ductal Carcinoma in Situ in The Male Breast: A Rare Entity.

Pure ductal carcinoma in situ of male breast (DCIS) is extremely rare. Only a few cases have been reported until now. Its treatment is not well established. Prognosis is as good as in women. In this study, we reported 3 cases of pure ductal carcinoma in situ in the male breast. The mean age of DCIS patients was 58.3 years. The main symptom was a breast mass. The median size of the tumor was 25 mm. Two patients had an axillary lymph node. The left side was reached in 2 cases. All of the patients underwent mastectomy. The histopathological assessment showed papillary, cribriform, and comedocarcinoma in situ. There was no evidence of invasive carcinoma. In one case, the DCIS was associated with Paget's disease of the nipple. One patient received hormonotherapy. The time of follow-up ranged between 6 and 117 months. One patient developed an invasive recurrence.

Kaposi's sarcoma of the larynx: an unusual location in an HIV-negative patient (a case report).

Head and neck involvement of Kaposi's sarcoma is rarely encountered, especially for the Mediterranean classic subtype. Here we report a case of non-AIDS related laryngeal Kaposi's sarcoma in a 77-year-old Tunisian man complaining of 4-month history of hoarseness and dysphagia. The patient underwent exclusive local radiotherapy with a prescription dose of 45 Gy delivered in 1.8 Gy daily fractions. He remained complaint-free for 3 months.

MARCKS protein overexpression is associated with poor prognosis in male breast cancer.

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.

Dermatofibrosarcoma Protuberans of the Breast in Man: An Extremely Rare Entity With a Review of the Literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma of soft tissue representing about 1% of all tumors. In addition, DFSP occurs commonly on the trunk and extremities, and only a few cases of DFSP have been observed on the breast. In men, only 11 cases, including this case, have been reported. In this article, we present a case of left breast DFSP that occurred in a 44-year-old man. The physical examination revealed a left breast tender mass, which invaded the skin. The tumor was staged as T4b N0 M0. Mammography and sonography showed a suspect mass of the left breast. The biopsy and immunochemistry permitted the diagnosis of DFSP of the left breast. The patient had a left mammectomy, with free margins. He presents no evident sign of recurrence 7 months later.

Forkhead box M1 (FOXM1) expression predicts disease free survival and may mediate resistance to chemotherapy and hormonotherapy in male breast cancer.

BACKGROUND: Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. OBJECTIVE: Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. METHODS: FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. RESULTS: Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P < 0.001). CONCLUSIONS: FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.

Prognostic implications of the intrinsic molecular subtypes in male breast cancer.

PURPOSE: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological features. METHODS: We retrospectively identified 130 MBC cases from 2004 to 2013. Intrinsic molecular subtypes were determined by immunohistochemistry (IHC). RESULTS: From a total of 130 MBC cases, 45.4% of tumors were luminal A subtype, 44.6% were luminal B, 5% were HER2 positive and 5% were triple negative tumors. There were statistically significant differences between different IHC intrinsic subtypes regarding tumor size (p=0.001), estrogen receptor (ER) status (p=0.001), progesterone receptor (PR) status (p=0.001), HER2 status (p=0.001) and Ki67 proliferation index (p=0.001). CONCLUSION: The distribution of breast cancer intrinsic subtypes in males is different compared to its female counterpart; however, they don't seem to give the same prognostic value.

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.

Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.

BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle. AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker. METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method. RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score. CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.

BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle. AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker. METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method. RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score. CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

[Gastric MALT lymphoma: anatomo-clinical data and outcome of early stage H. pylori-associated gastric MALT-lymphoma resistant to treatment]. / Lymphome du MALT gastrique : Particularités anatomo-cliniques et évolutives des formes résistantes au traitement.

AIM: To describe the clinical, endoscopic and histological particularities of early stage HP associated gastric MALT lymphoma resistant to anti Hp treatment and identify predicting factors of resistance. METHODS: We retrospectively studied 12 patients with primary low grade gastric localized MALT lymphoma treated with anti HP treatment and diagnosed at La Rabta Hospital from 1999 to 2009. RESULTS: The ultrasonography was normal in 5 patients between the 6 responding patients. Perigastric lymph nodes were found in non responders (33.3%). Hp eradication was achieved in 66% of patients not responding while Hp was eradicated in 100% of responders. The two non-responding patients with failure of eradication of Hp had a strain resistant to Clarithromycin Hp. CONCLUSION: Predicting factors of failure of anti HP: HP resistance to antibiotics, the proximal head, and the presence of perigastric lymph nodes. Recently, chromosomal aberrations and immune-histochemical markers have been implicated as factors of non response to anti Hp.