bromochloroacetic-acid and Breast-Neoplasms--Male

Molecular subtyping of breast cancer by gene expression has proven its significance in females. Immunohistochemical surrogates have been used for this classification, because gene expression profiling is not yet routinely feasible. Male breast cancer is rare and large series are lacking. In this study, we used immunohistochemistry for molecular subtyping of male breast cancer. A total of 134 cases of male breast cancer were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor (PR), HER2 and epidermal growth factor receptor (EGFR), as well as for CK5/6, CK14, and Ki67. HER2 was also assessed by chromogen in situ hybridization. Cases were classified as luminal A (ER+ and/or PR+, and HER2- and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 driven (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or CK14+ and/or EGFR+), or unclassifiable triple-negative (negative for all six markers). Luminal type A was by far the most encountered type of male breast cancers, representing 75% of the cases. Luminal type B was seen in 21% and the remaining 4% of cases were classified as basal-like (n=4) and unclassifiable triple-negative (n=1). No HER2 driven cases were identified. Patients with basal-like cancer were significantly younger (P=0.034). Luminal B type cancers showed significantly higher histological grade (P<0.001), mitotic index (P<0.001), and PR negativity (P=0.005) compared with luminal type A cancers. In conclusion, most male breast cancers are luminal A and luminal B types, whereas basal-like, unclassifiable triple-negative, and HER2 driven male breast cancers are rare. Luminal type B seem to represent a subtype with an aggressive phenotype. This distribution of molecular subtypes in male breast cancer is clearly different compared with female breast cancers, pointing to possible important differences in carcinogenesis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms, Male; ErbB Receptors; Humans; Immunohistochemistry; In Situ Hybridization; In Situ Hybridization, Fluorescence; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Protein Array Analysis; Receptor, ErbB-2; Receptors, Steroid

An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma, Intraductal, Noninfiltrating; Chromogranin A; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Membrane Proteins; Microfilament Proteins; Middle Aged; Neoplasm Recurrence, Local; Papilloma, Intraductal; Prognosis; Smooth Muscle Myosins

DNA microarray profiling studies have led to the classification of invasive breast carcinoma into luminal/estrogen receptor-positive, normal breast-like, Her2/neu-overexpressing, and basal-like types. Among these groups, the basal-like subtype is associated with the poorest clinical outcome in Western countries. To date, the clinicopathologic characteristics of the basal-like carcinomas, compared with other subtypes, have not been described in the Korean population. In this study, we used tissue microarray to examine the expression of basal cytokeratins (CK) (CK5 and CK14) and luminal CK (CK8/18), epidermal growth factor receptor, c-kit, hormone receptors (HRs), p53, and Her2/neu in 776 consecutive patients diagnosed with invasive breast carcinoma from January 1993 to December 1998 and categorized these cases into 5 subgroups (basal-like, HR-expressing, Her2/neu-overexpressing, HR and Her2/neu-expressing, and null subtypes negative for all markers), based on the immunohistochemical data. We identified cases of 114 (14.7%) basal-like, 345 (44.5%) HR-expressing, 133 (17.1%) Her2/neu-overexpressing, 61 (7.8%) HR and Her2/neu-expressing, and 123 (15.9%) null subtypes. Histologically, most basal-like breast cancers were invasive ductal carcinoma, not otherwise specified (98 cases, 86.0%), with high nuclear and/or histologic grades, and most metaplastic carcinomas (6 [75.0%] of 8 cases) were the basal-like subtype. Both basal-like and Her2/neu-overexpressing subtypes were associated with larger tumor sizes (mean, 3.6 and 3.3 cm, respectively) than the HR-expressing group (mean, 2.8 cm) (P = .001 and P = .036, respectively). Nodal stage of Her2/neu-overexpressing subtype was higher than that of basal-like subtype; however, overall stage was not different between the 2 groups (P = .010 and .123, respectively). Distant metastasis was most frequently observed in the Her2/neu-overexpressing subtype (33.8%), which was prognostically the worst subgroup of breast cancers. In contrast to previous findings from Western countries, our analyses reveal that the Her2/neu status is the most important prognostic factor of breast cancers.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Breast Neoplasms, Male; ErbB Receptors; Female; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Middle Aged; Phenotype; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Analysis; Tumor Suppressor Protein p53

The prognostic factors and expression of molecular markers in male breast carcinomas are similar to those in female breast cancers. The identification of distinct cytokeratin (CK) profiles (basal as opposed to luminal cells) helps to identify subsets of tumours with different clinical behaviour. The aim of this study was to investigate CK expression in male breast cancer.. Thirty-two cases of male breast cancer were studied. The panel of CKs studied by immunohistochemistry included: 5/6, 14, 17, 18 and 19. Pathological findings and CK expression were analysed in all cases. Histological patterns included ductal carcinoma in situ, invasive ductal carcinoma and mixed patterns. Four cases were positive for CK5/6 and CK14, identifying a basal-like phenotype. CK17 was negative in all but two cases. All cases expressing either CK5/6 or CK14 were invasive carcinomas of high nuclear and histological grade and were also larger compared with the tumours not expressing CK5/6 and CK14. All tumours except three (also negative for CK5/6) expressed CK18 and CK19. The four basal-like tumours were negative for Her-2 expression.. Male breast carcinomas have a basal-like phenotype that is similar in frequency to that of female breast carcinomas. The expression of CK5/6 and CK14 identifies a subset of pathologically aggressive male breast cancers.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis

No standard method for handling and histopathologic examination of the sentinel node (SN) exists. We hypothesized that a focused examination of all nodes with serial sectioning and cytokeratin immunohistochemical staining would confirm the SN as the node most likely to harbor metastasis. Intraoperative lymphatic mapping and sentinel lymphadenectomy using blue dye and (99m)technetium-labeled sulfur colloid were performed. All nodes were stained with H&E. All tumor-free nodes underwent additional sectioning and staining with H&E and an immunohistochemical stain. Routine H&E examination detected SN metastases in 27.6% of cases. Occult SN metastases were identified in 12.7% of cases. None of the 724 non-SNs examined contained occult metastases. The SN false-negative rate was zero. This study confirms histopathologically that the SN has biologic significance as the axillary node most likely to harbor metastatic tumor Standardization of the handling, sectioning, and staining of the SN is necessary as lymphatic mapping and sentinel lymphadenectomy become integrated into the care of patients with breast cancer

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms, Male; Carcinoma; Coloring Agents; Female; Humans; Immunohistochemistry; Keratins; Lymphatic System; Male; Middle Aged; Monitoring, Intraoperative; Radionuclide Imaging; Sentinel Lymph Node Biopsy; Technetium

Mammary Paget's disease unfrequently occurs in males, and may be pigmented in rare instances. Differential diagnosis with malignant melanoma relies on immunohistochemical studies.. A case of Paget's disease of the nipple in a 76 year-old male is reported, clinically mimicking a malignant melanoma because of massive pigmentation. Histologically, large Paget's clear cells were intermingled with numerous melanin-rich dendritic melanocytes. An underlying ductal carcinoma was found. After differential immunohistochemical staining, diagnosis of Paget's disease could be unequivocally substantiated since Paget's cells stained for epithelial markers, c-erbB-2 and hormonal receptors, whereas protein S100 and HMB45 were negative.. Pigmentation in mammary Paget's disease occurs preferentially in males. Pigmentation results from numerous melanocytes with abundant melanin in close contact with Paget's cells. An increased number of melanocytes may also be observed in cutaneous metastatic breast carcinomas. It could result from a chemotactic factor produced by neoplastic cells.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms, Male; Diagnosis, Differential; Genes, erbB-2; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Nipples; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms

We report the case of a 78-year-old man who developed a breast mass 12 months after hormonal therapy for palliation of prostatic adenocarcinoma. On histologic and immunohistochemical examination, the breast tumor revealed a unique collision tumor composed of metastatic prostatic adenocarcinoma and solid papillary breast carcinoma.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Breast Neoplasms, Male; Carcinoma, Papillary; Humans; Immunohistochemistry; Keratins; Male; Mastectomy, Radical; Neoplasms, Multiple Primary; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone

Topics: Actins; Aged; Aged, 80 and over; Antigens, CD34; Breast Neoplasms, Male; Desmin; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Muscle, Smooth; Neoplasms, Fibrous Tissue; Neoplasms, Muscle Tissue; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; Vimentin

Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Breast Neoplasms, Male; Carcinoembryonic Antigen; Female; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Mucin-1; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

Paget's disease of the breast is a rare condition with an incidence of 3% to 5% of all mammary malignancies. Of all malignant breast cancer, 1% occurs in male patients, and thus, Paget's disease of the male breast is extremely rare. We present a case of intraductal carcinoma of the male breast presenting as Paget's disease.

Topics: Aged; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Humans; Keratins; Male; Mastectomy, Simple; Mucin-1; Neoplasms, Multiple Primary; Nipples; Paget's Disease, Mammary

Pathologic examination of axillary lymph nodes (ALNs) may miss micrometastases in 30 per cent of breast cancer patients. We have developed a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR)-based screening method that detects histopathologically positive ALNs with a 5 per cent false-negative rate. The purpose of this study was to compare this RT-PCR methodology with histopathology with regard to sensitivity and cost. Pathologically negative ALNs from 35 breast cancer patients were re-evaluated by a single pathologist in a blinded fashion using serial sectioning with immunohistochemical staining. Histopathologic results were then compared with those of RT-PCR. Cost analysis was performed based on standard charges for these methods. RT-PCR identified micrometastases in 14 of 35 pathologically negative nodes. Serial sectioning and immunohistochemical staining identified micrometastases in two cases, with RT-PCR positive for one of these. The charge per specimen for performing routine histopathologic examination was $380, serial sectioning and immunohistochemical staining $787, and RT-PCR $125. RT-PCR appears to be more sensitive at detecting ALN micrometastasis than histopathologic examination even with serial sectioning and immunohistochemical staining. If micrometastatic breast cancer detected by RT-PCR proves to be clinically relevant, it could be a more effective screening methodology with significant cost savings as compared to currently available pathologic examinations.

Topics: Adult; Aged; Axilla; Biomarkers, Tumor; Biopsy; Breast Neoplasms; Breast Neoplasms, Male; Cost-Benefit Analysis; Female; Humans; Keratins; Lymph Node Excision; Lymph Nodes; Male; Mastectomy, Modified Radical; Mastectomy, Segmental; Middle Aged; Neoplasm Staging; Polymerase Chain Reaction; Sensitivity and Specificity