Molecular subtyping of male breast cancer by immunohistochemistry

Kornegoor, Robert; Verschuur-Maes, Anoek H J; Buerger, Horst; Hogenes, Marieke C.H.; Bruin, Peter C. de; Oudejans, Joost J.; Groep, Petra van der; Hinrichs, Bernd; Diest, Paul J. van

doi:10.1038/modpathol.2011.174

Cited by 118 publications

(122 citation statements)

References 39 publications

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“…All consecutive cases of surgical breast specimens of invasive male breast cancer from 1986 to 2011 were collected from four different pathology labs in the Netherlands (St. Antonius Hospital, Nieuwegein, Diakonessenhuis Utrecht, University Medical Center Utrecht, and Laboratory for Pathology East Netherlands), as described in more detail previously 1,9 and from three pathology labs in Germany (Paderborn, Cologne, Kassel). Hematoxylin and eosin (HE) slides were reviewed by four experienced observers (PJvD, RK, AM, ML) to confirm the diagnosis and to type and grade according to current standards.…”

Section: Patient Materialsmentioning

confidence: 99%

“…For all cases, hormone receptor and HER2 status were reassessed as described previously. 9 Tissue microarray (TMA) slides were used for immunohistochemical staining of ER, PR, and chromogenic in situ hybridization for HER2 assessment, the latter showing HER2 amplification in only five cases (3%). Most tumors were ER positive (131/145; 90%), and PR positivity was also common (97/145; 67%).…”

Section: Patient Materialsmentioning

confidence: 99%

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Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

et al. 2013

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Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n ¼ 112; P ¼ 0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.

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Section: Patient Materialsmentioning

confidence: 99%

Section: Patient Materialsmentioning

confidence: 99%

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

et al. 2013

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“…27 This group is composed of 134 consecutive cases from 1986 to 2010, collected from four different pathology labs in The Netherlands (St Antonius Hospital, Nieuwegein, n ¼ 28; Diakonessenhuis, Utrecht, n ¼ 22; University Medical Center Utrecht, Utrecht, n ¼ 23; and Laboratory for Pathology, East Netherlands, n ¼ 40) and two hospitals in Germany (Paderborn, n ¼ 8 and Cologne, n ¼ 13). The age ranged from 32 to 89 years (average: 66 years).…”

Section: Patient Materialsmentioning

confidence: 99%

“…12,15 Immunohistochemistry Immunohistochemical stainings were performed using tissue microarray (TMA) blocks, which were constructed as described before. 27 In short, hematoxylin-and eosin-(HE) stained slides were used to identify representative tumor areas. From the areas richest in tumor cells, three 0.6-mm punch biopsies from formalin-fixed and paraffin-embedded tissue blocks were obtained and embedded in a recipient paraffin block, using a precision tissue array instrument (Beecher Instruments, Sun Prairie, WI, USA).…”

Section: Fibrotic Focusmentioning

confidence: 99%

Fibrotic focus and hypoxia in male breast cancer

et al. 2012

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Fibrotic focus is a scar-like lesion near the center of a carcinoma and has been associated with high-grade, lymph node metastases and poor survival in female breast cancers. Hypoxia is suggested to be the crucial link between fibrotic focus and aggressive tumor phenotype and is also itself a poor prognostic marker. We here set out to study fibrotic focus and hypoxia in male breast cancer for the first time. In a group of 134 male breast cancer patients, the presence and size of a fibrotic focus and the expression of three hypoxia-related immunohistochemical stainings, hypoxia-inducible factor-1a, carbonic anhydrase IX and Glut-1 were studied in correlation with clinicopathological features and prognosis. Fibrotic focus was seen in 25% of the male breast cancer cases and was correlated with hypoxia-inducible factor-1a overexpression (P ¼ 0.023), high grade (P ¼ 0.005), high mitotic activity (P ¼ 0.005) and lymph node metastases (P ¼ 0.037). Hypoxia-inducible factor-1a-positive tumors were more often high grade (P ¼ 0.003) and HER2 amplified (P ¼ 0.005). Glut-1 expression was also more common in grade 3 tumors (P ¼ 0.038), but no association between carbonic anhydrase IX and any clinicopathological feature was found. Fibrotic focus 48 mm and hypoxia-inducible factor-1a overexpression were correlated with decreased patients' outcome (P ¼ 0.035 and 0.008, respectively). Hypoxia-inducible factor1a overexpression was an independent and the most powerful predictor of survival in multivariate analysis (P ¼ 0.029; hazard ratio 2.5). In conclusion, the presence of a fibrotic focus is associated with hypoxia-inducible factor-1a overexpression, and both are associated with aggressive tumor phenotype and poor survival in male breast cancer. These markers seem to have similar clinical importance as previously reported in female breast cancer. Modern Pathology (2012) 25, 1397-1404; doi:10.1038/modpathol.2012.101; published online 8 June 2012Keywords: fibrotic focus; hypoxia; male breast cancer; prognosis Male breast cancer is uncommon and represents o1% of all breast cancers. 1 Large series in male breast cancer are lacking and much of the knowledge is generalized from breast cancer in female subjects. The limited data published on male breast cancer indicate that there are genetic and phenotypic differences between male and female breast cancer. [2][3][4][5][6] Initially, prognosis in men was claimed to be poor with higher incidence of lymph node metastases at the time of discovery, but more recent studies showed that prognosis of male and female breast cancers corrected for stage and age is similar. [7][8][9] Although tumor size and lymph node status are independent prognosticators in male breast cancer, 9,10 there still is a need for more accurate outcome predictors of male breast cancer.A fibrotic focus is a scar-like lesion consisting of an area of mainly collagen and fibroblasts, often located near the center of a carcinoma. Fibrotic focus is associated with poor survival in female breast cancer and with high grade, hig...

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“…This group of patients was previously used to analyze the molecular sub-typing, fibrotic focus and hypoxia in male breast cancer. 14,15 The patients for whom survival data was not available were excluded in the current study. Age, tumor size and lymph node status were extracted from the pathology reports.…”

Section: Patientsmentioning

confidence: 99%

Prognostic value of automatically extracted nuclear morphometric features in whole slide images of male breast cancer

Veta¹,

Kornegoor

Huisman

et al. 2012

Modern Pathology

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Numerous studies have shown the prognostic significance of nuclear morphometry in breast cancer patients. Wide acceptance of morphometric methods has, however, been hampered by the tedious and time consuming nature of the manual segmentation of nuclei and the lack of equipment for high throughput digitization of slides. Recently, whole slide imaging became more affordable and widely available, making fully digital pathology archives feasible. In this study, we employ an automatic nuclei segmentation algorithm to extract nuclear morphometry features related to size and we analyze their prognostic value in male breast cancer. The study population comprised 101 male breast cancer patients for whom survival data was available (median follow-up of 5.7 years). Automatic segmentation was performed on digitized tissue microarray slides, and for each patient, the mean nuclear area and the standard deviation of the nuclear area were calculated. In univariate survival analysis, a significant difference was found between patients with low and high mean nuclear area (P ¼ 0.022), while nuclear atypia score did not provide prognostic value. In Cox regression, mean nuclear area had independent additional prognostic value (P ¼ 0.032) to tumor size and tubule formation. In conclusion, we present an automatic method for nuclear morphometry and its application in male breast cancer prognosis. The automatically extracted mean nuclear area proved to be a significant prognostic indicator. With the increasing availability of slide scanning equipment in pathology labs, these kinds of quantitative approaches can be easily integrated in the workflow of routine pathology practice.

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Molecular subtyping of male breast cancer by immunohistochemistry

Cited by 118 publications

References 39 publications

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

Fibrotic focus and hypoxia in male breast cancer

Prognostic value of automatically extracted nuclear morphometric features in whole slide images of male breast cancer

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