Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes.

Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies.

The impact of body mass index and nuclear ß-catenin on survival in locally advanced rectal cancer treated with preoperative radiochemotherapy.

BACKGROUND AND OBJECTIVE: We examined the prognostic value of obesity and nuclear ß-catenin in patients with locally advanced rectal cancer. METHODS: We prospectively recruited a total of 98 eligible patients with locally advanced cancer for preoperative radiochemotherapy followed by total mesorectal excision. Patients' height and weight were reaorded before radiochemotherapy, and the immunohistochemical expression of nuclear ß-catenin was analyzed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier method and a Cox regression model was employed for the multivariate analysis. RESULTS: Obese patients were associated with a lower number of recurrences (3.6% vs. 34.3%, P = 0.001), and a higher DFS (95% vs. 53%; HR, 0.09; 95%CI, 0.01-0.64; P = 0.005) than non-obese patients. In the multivariate analysis, body mass index, nuclear ß-catenin expression, and the absence of lymph node metastases showed a significant increase in DFS. CONCLUSIONS: Obesity and nuclear ß-catenin are independent favorable prognostic factors for DFS in locally advanced cancer treated with preoperative radiochemotherapy. J. Surg. Oncol. 2017;115:301-306. © 2017 Wiley Periodicals, Inc.

Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index.

INTRODUCTION: Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes. METHODS: Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2−, Ki-67 <14), luminal B (ER + and/or PR+, HER2−, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER−, PR−, HER2−, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2−, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2−, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER−, PR−, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER−, PR−, HER2−, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER−, PR−, HER2−, any Ki-67, CK 5/6−, EGFR−). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value. RESULTS: Luminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months. CONCLUSIONS: Each intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.

Male breast cancer: immunohistochemical subtypes and clinical outcome characterization.

AIM: The aim of this study was to assess the molecular subtype profiles of male breast cancer (MBC) and subsequent clinical outcome using a validated 6-marker immunohistochemical panel. METHODS: A total of 43 cases of MBC were examined retrospectively using a semiquantitative immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (Her2), epidermal growth factor receptor and cytokeratin 5/6. Patients were classified into the following categories: luminal A, luminal B, Her2-positive or basal-like subtypes. RESULTS: The median age of patients was 63 years (r: 32-89). The predominant histology was invasive ductal carcinoma (91%). Only 1 patient had advanced breast cancer at diagnosis. Ninety-three percent were ER-positive and 84% were PR-positive. Two patients had tumors that were ER- and PR-negative. The distribution of tumor molecular subtypes was 19 (44%) luminal A, 22 (51%) luminal B and 2 (5%) basal-like. The Her2-positive tumor subtype was not identified. The clinicopathological characteristics did not differ significantly between tumor subtypes A and B. There were no significant differences in 6-year disease-free survival (74 vs. 82%, p = 0.77) or overall survival (74 vs. 82%, p = 0.69) between luminal A and luminal B subtypes, respectively. CONCLUSION: The most common subtypes in our cohort of MBC were luminal B followed by luminal A, and no differences were found between both tumor subtypes in terms of clinicopathologic characteristics and patient outcome.

Stromal expression of vascular endothelial growth factor C is relevant to predict sentinel lymph node status in melanomas.

The dissemination of tumour cells to the lymph nodes is a complex process involving the formation of new lymph vessels, or lymphangiogenesis, produced by the tumour itself. The main growth factor involved in lymphangiogenesis is vascular endothelial growth factor C (VEGF-C), which is secreted by several different malignant tumours, including melanoma. Not only has VEGF-C expression been found in tumour cells, it has also been detected in tumour stromal cells like macrophages and fibroblasts. This study aimed to determine whether the expression of VEGF-C in tumour and stromal cells in cutaneous melanoma determines lymphangiogenesis and neoplastic dissemination to lymph nodes. We examined cases from 50 patients with melanoma who underwent selective biopsy of the sentinel lymph node. Immunohistochemical study was done with D2-40 to label lymph vessels, and the expression of VEGF-C was evaluated in tumour and stromal cells. Lymph vessel density was greater in sentinel lymph node-positive than in sentinel lymph node-negative cases, though the difference was not significant (P = 0.075). A significant correlation was seen between lymph vessel density and tumour thickness and the presence of ulceration. The main finding was that the expression of VEGF-C in fibroblasts was highly associated with the presence of metastasis in the sentinel node and with the Clark level. However, VEGF-C expression showed no relation in either tumour cells or macrophages with node status or other prognostic factors, such as the Breslow index or Clark level. Our results highlight the relevance of the stroma in tumour progression in cutaneous melanoma and its role in the spread to lymph nodes.

[Seminoma and teratocarcinoma: synchronic unitesticular presentation as independent nodules with different histologies? Ultrasound characteristics]. / Seminoma y teratocarcinoma: presentación sincrónica monotesticular como nódulos independientes con distintas histologías? Caracteres ecográficos.

OBJECTIVE: To describe the ultrasound characteristics, vascularization pattern (colour Doppler ultrasound) and possible histogenesis of one case of synchronic untesticular seminoma and teratocarcinoma as independent tumor nodules, histologically different, in a 19-year-old patient with testicular mass for eight months. METHODS: Conventional ultrasound, colour Doppler ultrasound, and high resolution Doppler angiogram were performed, analyzing vascular flows. After resection of the tumor, macroscopic and histological sections were related with ultrasound images. RESULTS: The patient showed three independent, well limited, tumoral nodules in the right testicle: two of them heterogeneous, 20 and 33 mm in diameter, with cystic areas and calcifications. The third nodule was solid, hypoechoic and homogeneous, 26 mm in diameter. All nodules presented an increase in vascularization with low resistance arterial flows. Histologically the first two nodules were teratocarcinomas (predominantly mature teratoma and embryonal carcinoma) and the third classic seminoma. CONCLUSIONS: Although seminoma and mixed germ cell tumors are common, "their presentation in the some testicle as independent nodules with different histologies is a rarely referred case in the literature, which allows us to apply a histogenetic and ultrasound-pathologic correlation model in seminomatous and nonseminomatous tumors. The presence of cystic cavities and gross calcifications is highly correlated with teratoma. In our case there are not significant differences in the vascularization pattern with Doppler ultrasound.