Interphase Cytogenetics of Male Breast Cancer

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  • 2005 Blackwell Publishing, Inc., 1075-122X/05The Breast Journal, Volume 11 Number 6, 2005 532533

    Blackwell Publishing, Ltd.


    Interphase Cytogenetics of Male Breast Cancer

    To the Editor:Male breast cancer is 100 times less common than its

    female counterpart and accounts for less than 1% of allcancers in men (1). Chromosomal aberrations identifiedin male breast carcinomas that are known also to occurrepeatedly in similar tumors in women are del(1)(q11),17, 18, and 11. Furthermore, the only recurrent structuralchromosome abnormality detected up to now in malebreast carcinomas, del(18)(q21), is not common in carci-nomas of the female breast.

    Other nonrandom, numerical chromosome abnormal-ities are also apparent (loss of the Y chromosome, trisomyfor chromosome 5, and gain of an X chromosome). Thatan X chromosome is preferentially gained in breast carci-noma cells in men is particularly interesting in view of thefact that patients with Klinefelters syndrome, whoseconstitutional karyotype is 47,XXY, have a high risk ofdeveloping breast cancer (2).

    Synchronous bilateral breast carcinoma is an infre-quent presentation, especially in the male (3). The pres-ence of bilateral breast cancer is therefore a clinical cluesuggesting the presence of an inherited susceptibility tobreast cancer (4)

    The aim of this study was to establish the cytogeneticprofile of male breast cancer patients. Fluorescence in situhybridization (FISH) was applied to interphase nucleito detect numerical chromosome changes in two benigngynecomastias and one malignant breast carcinomaderived from three Egyptian patients with male breastdisease (two synchronous bilateral breast carcinomas[one malignant and one benign from the same patient]).

    In this study, lymphocyte nuclei were used as a control.Cutoff values were determined based on the mean + 3 SD.FISH analysis of touch prints derived from the three exam-ples of male breast diseases demonstrated chromosomalaberrations. The FISH results of patient 1 showed loss ofchromosome 17 and overrepresentation of chromosomes8 and 11. Gain of X chromosome was also detected.Patient 2 (left benign gynecomastia) showed underrepre-sentation of chromosome 17 and an increased copy num-ber involving chromosome 8. Loss of the Y chromosome

    and gain of chromosome 5 was also demonstrated. Patient2 (ductal carcinoma) presented with overrepresentationof chromosomes 1, 8, and 17.

    We identified the involvement of particular chromo-somes in proliferative benign male breast lesions andconfirmed that the genetic aberrations present in maleand female breast cancer are very similar. Gains involvingchromosome 8 were detected in all cases by FISH. In addi-tion, invasive ductal carcinoma (patient 3) showed a highfrequency of trisomy of chromosome 8. An increased copynumber of chromosomes 8 has been described in prostatecancer (5), head and neck carcinomas (6), female infiltra-tive ductal carcinoma (7), fibroadenomas (8), and malebreast cancer (9). Most, if not all types of human malignancyhave been reported to have amplification or overexpres-sion of the


    gene (mapped on 8q24), although thefrequency of these alterations varies greatly among differ-ent reports (10). Many of the genetic aberrations sharedby female and male breast cancers are also shared bybreast cancer and other epithelial cancer types (11). It ispossible that the overrepresentation involving 8q is anexample of these genetic changes.

    Alterations involving chromosome 1 were detected inone of our samples (ductal carcinoma). Partial loss of 1qwas described in 1 of 14 cytogenetically examined cases ofmale breast cancer published thus far (12). Alterationsinvolving overrepresentations on 1p have been describedin both female and male breast cancer. The high frequencyof aberrations observed suggests that some regions ofchromosome 1 may be involved in the pathogenesis ofbreast cancer.

    The FISH analysis of patient 3 showed a gain of chro-mosome 17. This result confirmed the alteration previouslydescribed by G-banding analysis (12). Amplification andpolysomy of chromosome 17 is often found in femalebreast cancer (10). In one of our patients, the loss of Y wasobserved in a significant proportion of tumor cells, alwaysassociated with other numerical and structural anomalies.Loss of the Y chromosome was found in 3 of 10 publishedcases (13). The significance of the loss of a Y chromosomein tumor tissue or in normal cells from elderly men hasbeen discussed extensively and may be associated withage, coincidental or related to an accelerated turnover ofcells (as in tumor cells), or indicative of a clonal anomaly.

  • Letter to the Editor


    The gain of an X chromosome was observed in patient 1and in two published cases (14,15). Because breast canceris a sex hormone-dependent malignancy, the loss or gainof a sex chromosome in tumor cells may be related totumor progression.

    Other changes observed in our patients and describedelsewhere in regard to male breast cancer are the gain ofchromosome 5 that occurred in 2 of 10 published cases(16,17) and in patient 2 of this report. The natural historyof male breast carcinomas has been described in a limitednumber of studies (18,19). The studies published so farshow a number of similarities in the pattern of cytogeneticand CGH alterations in female and male breast prolifera-tive diseases, suggesting a common etiology for the diseaseprocess in both sexes.

    Magdy Sayed Aly, PhDDepartment of Zoology, Faculty of Science, Cairo

    University (Beni-Suef Branch), Cairo, Egypt


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