Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient without any detectable BRCA2 germline mutation

Two synchronous bilateral breast carcinomas and their matched lymph node metastases from a 70-year-old man were cytogenetically analyzed. All four tumors were near-diploid, and except for the primary tumor from the right breast, had a 45,X,-Y clone in common. The loss of the Y chromosome was, however, common to all four tumors, whereas metaphase cells from peripheral blood lymphocytes showed a normal 46, XY chromosome complement. The primary tumor from the right breast was monoclonal, with loss of the Y chromosome and gain of 1q, whereas its metastasis had two related clones: the 45,X,-Y clone, and the other a more complex version of the clone in the primary tumor, with inv(3), -14, and del(16)(q13) as additional changes. The primary tumor from the left breast was polyclonal with three unrelated clones: 45,X,-Y/45,XY,-18/47,XY,+20, two of which were present in its metastasis. DNA flow cytometric studies showed diploidy for both primary tumors. No mutation in the BRCA2 gene was found on analysis of DNA from peripheral blood lymphocytes. The present findings show that del(16)(q13) is a recurrent finding among male breast carcinomas and that some of the primary cytogenetic abnormalities, as well as the pattern of chromosomal changes during the progression of sporadic breast carcinoma in the male, are similar to those in the female. In addition, the loss of the Y chromosome in the tumors but not in peripheral blood lymphocytes, suggests a possible role for this abnormality in the pathogenesis of male breast carcinoma.     

On the significance of trisomy 7 and sex chromosome loss in renal cell carcinoma

Cytogenetic analysis of 30 renal cell carcinomas showed 3p aberrations in nine tumors, trisomy 7 in 17 tumors, and clonal loss of one sex chromosome in 14 tumors. The 3p aberrations and trisomy 7 were present in the same clone in two tumors and in separate clones in three tumors. Loss of one sex chromosome was present together with 3p aberrations in the same clone in one tumor and occurred in seemingly unrelated clones in two tumors. It occurred as the sole change in five tumors. Clones with trisomy 7 as the only change were present in six tumors. Trisomy 7 and loss of one sex chromosome were present in separate clones in four tumors and in the same clone in one tumor. Because +7 and -X/-Y were thus rarely present together with clonal structural abnormalities, in particular 3p changes, our findings make it highly unlikely that loss of one sex chromosome or trisomy 7 represents a primary change in renal cell carcinoma. We instead suggest that there is a tendency for normal kidney cells to lose an X or a Y chromosome and also to gain an extra copy of chromosome 7. This tendency is retained by renal carcinoma cells; therefore, trisomy 7 and sex chromosome loss should not be viewed as tumor-specific abnormalities in this context. Whether these simple numerical aberrations reflect in vivo mosaicism or are acquired in vitro remains unresolved.     

Karyotypic findings in two cases of male breast cancer

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.     

Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast

Interstitial deletions of the short arm of chromosome 3 were found in short-term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p– coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis. © 1993 Wiley-Liss, Inc.     

Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.     

Comparative genomic hybridization analysis of benign and invasive male breast neoplasms

Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3 through pter, 11p14 through q12, and 17p11.2 through qter, and loss of 1q41 through qter and 4q33 through qter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2 through qter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer.     

Comparison of alterations of chromosome 17 in carcinoma of the ovary and of the breast

 Breast and ovarian carcinomas share a region of allelic loss on chromosome 17q25, suggesting that these tumours may arise by similar molecular pathways. We analysed paraffin-embedded tissues from 84 sporadic ovarian carcinomas and 42 sporadic infiltrating ductal carcinomas of the breast for abnormalities on chromosome 17. Loss of heterozygosity (LOH) of at least one informative marker on 17q was identified in 49 of 82 (60%) ovarian carcinomas, as against only 6 of 40 (15%) informative breast carcinomas (P<0.0001). In ovarian carcinoma, LOH was most commonly observed for GH on 17q23 (56%), and was also frequently observed at 17q21 (46%). In contrast, LOH of D17S1330/CTT16 on 17q25 was observed in only 19% of ovarian tumours. LOH in breast carcinomas was most frequently observed at 17q21 (16%), less frequently at 17q23 (7%) and not identified at all at 17q25 in any breast cancers. Immunohistochemical analysis demonstrated overexpression of the p53 gene product in 38 of 84 (45%) ovarian carcinomas, as against 10 of 42 (24%) breast carcinomas (P=0.0195). p53 immunoreactivity was significantly associated with LOH in ovarian and breast cancers. Immunohistochemical expression of HER2/neu was observed in 6 of 84 (7%) ovarian and 3 of 42 (7%) breast carcinomas. There was no relationship between HER2/neu immunoreactivity and LOH. Although sporadic carcinomas of breast and ovary share some regions of allelic loss on chromosome 17q, differences in other alterations on this chromosome suggest divergent pathways of tumour development. Received: 8 July 1998 / Accepted: 6 January 1999     

Cytogenetic analysis of six renal oncocytomas and a chromophobe cell renal carcinoma. Evidence that -Y, -1 may be a characteristic anomaly in renal oncocytomas.

Renal oncocytomas are benign tumors whose morphologic features may sometimes be confused with those of certain low-grade malignant neoplasms of the kidney, e.g., chromophobe cell and granular cell variants of renal carcinoma. The presence of a specific genetic abnormality might help differentiate these tumors. Because very few cytogenetic studies of renal oncocytomas have been published, we investigated a consecutive series of six such tumors. We also performed chromosome analysis on a chromophobe cell carcinoma because cytogenetic analyses of this tumor have not been previously reported. Tumor cell metaphases were analyzed after mechanical and enzyme disaggregation, in situ culture, and robotic harvesting. Clonal abnormalities were present in five of the six oncocytomas, and loss of chromosome 1 with loss of the Y chromosome occurred in two. Review of the literature disclosed four other renal oncocytomas with the 44,X,-Y,-1 karyotype. In the chromophobe cell carcinoma, we noted an abnormal clone with a del(11)(p12p15.1); similar anomalies were not observed in the renal oncocytomas. We conclude that renal oncocytomas have clonal chromosome abnormalities and that a subgroup of these tumors may be specifically associated with loss of chromosomes 1 and Y. Because this is a small series, further investigation may help establish whether cytogenetic studies can provide diagnostic and pathogenic information about renal oncocytomas.     

Discrimination between multicentric and multifocal breast carcinoma by cytogenetic investigation of macroscopically distinct ipsilateral lesions

Whether macroscopically distinct carcinomas in the same breast are clonally related (multifocal breast carcinoma) or unrelated (multicentric breast carcinoma) is no longer only a scientific-pathological issue but, because different therapeutic strategies may be preferable for cases with intramammary metastatic disease compared with cases of multiple primary breast carcinomas, one that may have profound clinical implications. We studied the evolutionary relationship among macroscopically distinct, ipsilateral breast carcinomas by cytogenetic analysis of 26 tumorous lesions from 12 patients. Sixteen of the 26 foci (62%) were found to contain clonal chromosome abnormalities. Two carcinoma foci were karyotypically abnormal in each of seven patients. Four of these cases had an evolutionarily related, cytogenetically abnormal clone in the two lesions from the same breast, whereas the remaining three cases had completely different clonal karyotypic aberrations in the separate foci. These results, together with our previous findings in five other informative cases, show that multiple, synchronous breast tumors sometimes arise through intramammary spreading of a single primary carcinoma, whereas on other occasions they are the result of the simultaneous emergence of pathogenetically independent carcinomas within the breast. In the total material, an association was seen between the proximity of the foci and the likelihood of them being karyotypically related. Genes Chromosom. Cancer 18:170–174, 1997. © 1997 Wiley-Liss, Inc.     

Cytogenetics of breast cancer

Chromosome counts were performed on 1,100 cells from 17 malignant breast carcinomas and on 168 cells of four normal tissue samples after amethopterin treatment and G-banding. Karyotypes were established from 216 cells of 11 tumor-derived cultures and from 47 cells of four nonmalignant tissue-derived cultures. Karyotypes of cells from nonmalignant samples showed a normal diploid chromosomal constitution with no consistent loss or gain of a specific chromosome. Structural chromosomal abnormalities were not observed. Tumor-derived cultures could be distinguished from normal cultures on the basis of a significantly increased incidence of numerical changes and structural chromosomal aberrations. In nine of 11 tumor-derived cultures, numerically normal cells were shown to be pseudodiploid, with frequencies ranging to 43% (mean, 13.2%) of the diploid cells. In agreement with previous reports, cytogenetic analyses showed predominantly diploid cells. Clonal numerical changes of chromosomes 17, 18, 20, and 21 could be detected in three tumor samples. Clonal structural abnormalities could be observed in two of 11 analyzed tumours. A t(6;12)(p21;p13) and an enlarged chromosome 7 (7q+) were found in a patient with invasive ductal carcinoma. An inversion of chromosome 7 [inv(7)(q11.2q32)] was observed in one case, also diagnosed as invasive ductal carcinoma. The significance of these findings in relation to clinical data is discussed.     

Cytogenetic findings in 31 papillary thyroid carcinomas

Chromosome studies performed on 3I papillary thyroid carcinomas (PTCs) revealed clonal numerical and structural abnormalities in I2 tumors. The numerical clonal aberrations found were trisomy 2, trisomy 7, and loss of the Y chromosome. A nonrandom telomeric association, tas( I5; I6)(p I3; p I3), was observed in one carcinoma. Structural alterations with a breakpoint at I0q II.2 were detected in two tumors. Other chromosomes involved in rearrangements were chromosomes I, 2, 3, 5, 7, 9, II, 12, and 14. The observation of clonal changes of chromosome 2 [i(2)(qI0) and trisomy 2] in two tumors, which were both histologically classified as tall-cell PTC variants, suggests that gain of 2q may be important in the development of this morphological variant. © 1995 Wiley-Liss, Inc.     

Numerical aberrations of chromosome 9 in bladder cancer. A possible prognostic marker for early tumor recurrence

Bilharzial bladder cancer is one of the most common types of malignancy in both men and women in several developing countries including Egypt. It has several unique clinical, epidemiological, and histological characteristics, suggesting that it is an entity distinct from bladder cancer seen in Western countries. Genetic alterations in bilharzial-related bladder cancer have been studied infrequently, especially in the advanced stages of disease, that is, T3 and T4 classifications. The objective of this study was to extend establishing the baseline cytogenetic profile of this type of malignancy to early T1 and T2 classifications. For this purpose, fluorescence in situ hybridization was applied to interphase nuclei of frozen-stored samples with biotinylated repetitive DNA probes specific for all chromosomes to detect numerical chromosome changes in 35 patients presenting with relatively early-stage pT1 and pT2 disease. Eleven cases had squamous cell carcinoma (SCC) and 24 had transitional cell carcinoma. Six of 24 transitional cell carcinomas had diploid chromosome counts with all the probes. Numerical chromosome aberrations were detected in 18 cases (75%). In 12 cases, a loss of chromosome 9 was observed. In three cases, an additional loss of chromosome 17 was detected. One case demonstrated a loss of chromosome 10, whereas another two cases showed a gain of chromosome 7, next to a loss of chromosome 9. Loss of chromosome Y was observed in nine of the 27 male cases studied (33.3%), in which only one case showed an abnormality whereas four cases were detected next to loss of chromosome 9, and one case showed gain of chromosome 7. Five cases showed loss of chromosome 19 whereas gain of chromosome 4 was detected in two cases. Two of 11 samples of SCC had normal diploid chromosome counts with all the probes used. In four of 11 cases (36.4%) underrepresentation of chromosome 9, compared with the other chromosomes, was detected. An additional loss of chromosome 17 and gain of chromosome 7, next to loss of chromosome 9, was detected in three cases. One case showed loss of chromosome 17 as the only numerical aberration. Loss of the Y chromosome was detected in three cases of which one case had gain of chromosome 7 and one case had loss of chromosome 19. No correlation was found between any of the clinicopathologic parameters examined in this study and the presence or absence of any numerical chromosomal aberrations except for the significant association between schistosomal history and loss of Y chromosome (P=0.007).     

Structural and numerical aberrations of chromosome 22 in a case of follicular variant of papillary thyroid carcinoma revealed by conventional and molecular cytogenetics

This study reports a case of papillary carcinoma with vesicular components showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22 and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22 changes as the sole abnormality were seen. The main abnormal clone lacked the whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell population with a der(17)t(?17;22). Some of these chromosome 22 alterations have been described in other solid tumors such as meningiomas and neurinomas, suggesting a common genetic pathway of tumor progression occurring in a multistep process. Chromosome 22 changes do not seem to be involved in pure papillary thyroid tumors and therefore could be related to the maintenance of a follicular-type histological pattern.     

TP53 mutations are associated with a particular pattern of genomic imbalances in breast carcinomas

TP53 mutations play an important role in the development of several cancers and are present in 20-40% of all breast carcinomas, contributing to increased genomic instability. In order to address the relationship of mutated TP53 to genomic complexity, the present study analysed 61 breast carcinomas for TP53 mutations and compared mutation status with the pattern of genomic imbalances as assessed by comparative genomic hybridization (CGH). Twenty per cent of the present series of breast carcinomas harboured TP53 mutations. An increasing number of abnormalities, as identified by CGH (higher genomic complexity), correlated significantly with mutant TP53. Among the chromosome arms most commonly altered (in more than 20% of the tumours), loss of 8p and gain of 8q were associated with TP53 mutations, whereas loss of 16q was associated with wild-type TP53. By performing supervised hierarchical clustering analysis of the CGH data, a cluster of chromosome imbalances was observed that showed differences between wild-type and mutant TP53 cases. Among these, loss of chromosome arm 5q revealed the strongest correlation with altered TP53. To investigate further the most commonly deleted region of 5q, gene expression patterns from two publicly available microarray data sets of breast carcinomas were evaluated statistically. The expression data sets identified potential target genes, including genes involved in ubiquitination and the known TP53 target CSPG2. The genomic complexity of breast carcinomas as assessed by CGH is associated with TP53 mutation status; breast cancers with TP53 mutations display more complex genomes than do those with wild-type TP53. The pattern of genomic imbalances associated with mutant TP53 is non-random, with loss of chromosome arm 5q being particularly closely associated with TP53 mutations.     

Genomic alterations in tubular breast carcinomas

Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers.     

Cytogenetic characterization of 22 human renal cell tumors in relation to a histopathological classification.

In this study, cytogenetic and fluorescence in situ hybridization analyses were performed on 22 sporadic, unilateral primary renal cell tumors. The tumors were classified according to cell types, growth patterns, and grades of malignancy. A feeder layer technique was used for the cell culture of 13 clear-cell carcinomas, 4 chromophilic carcinomas, 3 chromophobe carcinomas, 1 oncocytoma, and 1 spindle-shaped pleomorphic carcinoma. Eighty-six percent (19/22) of renal tumors showed clonal abnormalities. The most frequent finding in the 15 male patients was loss of chromosome Y (9/15). In 3/15, it was the only observed aberration. The second most visible aberration was regional loss or entire loss of chromosome 9, which was detected in 36% (8/22) of the cases. Four cases showed loss of chromosome 9 and 4 cases a deletion of the short arm with breakpoints on 9p11 and 9p21. Loss of 3p material was observed in 32% (7/22) of the cases but only in 2/13 patients with clear-cell carcinoma. Gain of chromosome 12 or 12p was observed in 27% (6/22). In 23% (5/22) of the patients, gain of whole or partial chromosomes 2, 5, and 7 was found. Less-frequent findings were loss of chromosomes 8, 14, and 21; gain of chromosome 16; and structural abnormalities of chromosome 1 (each 18%; 4/22). Only some of the karyotypes described as typical for the various renal tumor types were confirmed. In contrast with previous reports, chromosome 3 and 9 aberrations did not allow differentiation between tumor types in our study.     

Cytogenetic characterization of tumors of the vulva and vagina

Neoplasms of the vulva and vagina account for less than 5% of all female genital tract cancers. Squamous cell carcinoma (SCC) represents more than 70% of the cases in both locales, followed by melanoma, basal cell carcinoma, Paget's disease, and other carcinoma subtypes. Until recently, only few cases had been analyzed by chromosome banding techniques and karyotyped, and also the number subjected to molecular cytogenetic analysis remains low. To understand better the genetic changes harbored by the neoplastic cells in cancer of the vulva and vagina, we analyzed cytogenetically 51 such tumors, finding karyotypic abnormalities in 37. All tumors were analyzed by G-banding, sometimes supplemented by multicolor fluorescence in situ hybridization, and a subset of tumors was also analyzed by comparative genomic hybridization. The two cytogenetically abnormal cases of Paget's disease both had two clones, one with gain of chromosome 7 as the sole change, the other with loss of the X chromosome among, in one case, other aberrations. The four cytogenetically abnormal malignant melanomas (three of the vulva, one of the vagina) presented complex karyotypes with aberrations involving different chromosomes but most often chromosome 1, specifically 1p12-q41. In the 31 cytogenetically abnormal SCCs, different clonal karyotypic abnormalities were seen. Intratumor heterogeneity with multiple clones was observed in 11 cases. The clones were cytogenetically unrelated in eight tumors but related in three, indicating that in the latter clonal evolution had taken place from a single malignantly transformed cell. The main chromosomal imbalances were gains of, or from, chromosome arms 3q, 5p, 8q, 9q, and 19q, and loss from 11q. Breakpoint clusters were seen in 11q13-23, 2q22-35, and 19q13, as well as in the centromeres and pericentromeric bands of chromosomes 3, 8, 9, 13, 14, and 22.     

Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands

The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary glands are described. Clonal numerical deviations as the sole anomaly were detected in four cases and structurally rearranged stemlines and sidelines in four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in one case the translocation was part of the abnormal stemline and in the other case it was the sole anomaly in a single variant cell. A similar or identical t(6;9)(q21-24;p13-23) has recently been reported in three of 15 previously published cases of ACC. The three remaining tumors with abnormal stemlines all had rearrangements of chromosome 9, including t(1;9)(q21;p21-22), der(9)i(9)(q10)inv(9)(q12q 13), and der(X)t(X;9)(p21;p22-23), respectively. The latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal clones present in this tumor. In addition to other abnormalities, the clone with der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ hybridization (FISH) was used for further characterization of the marker chromosomes. A survey of the present findings together with previous results from 15 ACC clearly demonstrates that rearrangements of 6q21-24 (deletions or translocations in 11 cases), 9p13-23 (translocations in seven cases), and 17p12-13 (translocations in three cases) are recurrent, and often primary, in ACC, and that the t(6;9)(q21-24;p13-23), found in five tumors, is a non-random, primary aberration. Genes Chromosom Cancer 10:115–121 (1994). © 1994 Wiley-Liss, Inc.     

Chromosomal rearrangements in Barrett's esophagus. A premalignant lesion of esophageal adenocarcinoma

Cytogenetic analysis of 15 short-term cultures of Barrett's esophagus were investigated. In five cases, the number of metaphases identified were insufficient for analysis. Of the remaining ten cases, nine contained clonal chromosome abnormalities. Of these nine cases, one demonstrated a structural chromosome rearrangement, t(3;6)(q21;p23); one case demonstrated trisomy for chromosomes 5 and 7; and seven cases demonstrated loss of the Y chromosome as a clonal change. Our results demonstrate that Barrett's esophagus is frequently characterized by clonal proliferation of karyotypically abnormal cells.     

Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men.

Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men.