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Biomedical subjects

J A Andersen

Publications and source records attributed to J A Andersen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clonal heterogeneity in breast cancer: karyotypic comparisons of multiple intra- and extra-tumorous samples from 3 patients.

Intratumor phenotypic heterogeneity is one of the characteristics of breast carcinomas, and genetic mechanisms are likely to contribute to it. We have studied breast cancer clonal heterogeneity by cytogenetic analysis of multiple tumor samples (one from each tumor quadrant) as well as samples of macroscopically normal surrounding breast tissue from 3 patients with this disease. Clonal chromosome aberrations were found in all 8 successfully analyzed samples from the carcinomas. Two to 6 cytogenetically unrelated clones were detected in each case, unevenly distributed among the tumor quadrants. Karyotypic abnormalities were also found in 4 out of 9 macroscopically tumor-free samples from the surrounding tissue; in 2 of these samples, a ductal carcinoma in situ was detected histologically, and the cytogenetic evidence suggests that the remaining 2 samples also contained neoplastic cells. Quantitative analysis of the findings revealed a statistically significant higher frequency of karyotypically abnormal cells in samples with a histologic diagnosis of carcinoma vs. samples without any detected malignancy. That cells bearing cytogenetic evidence that they belong to the tumor parenchyma are left behind during breast-conserving surgery for carcinoma of the breast may account for the relatively high long-term local relapse rates seen in this disease.

Adult↗
PubMed1995

DNA analysis of in situ ductal carcinoma of the breast via flow cytometry.

Flow cytometric (FCM) DNA analysis of 41 clinical cases of ductal carcinoma in situ (DCIS) of the breast was performed on fine-needle aspirates of unfixed, frozen tissue. Based on analysis of a single tissue sample, abnormal DNA content was found in 35 (85%) of the cases, and 15 (37%) disclosed heterogeneity. If five or more samples were analyzed, then heterogeneity was found in eight of ten cases. No conclusive correlation could be found between DNA index (DI) and histopathology. Our results on DCIS demonstrate a very high concordance with invasive breast cancer with respect to the frequency of DNA nondiploid cases, distribution of DI, occurrence of multiple clones, and S-phase fraction. This indicates that major genetic alterations and DNA heterogeneity are early events in carcinogenesis that are already established at the preinvasive stage.

Breast Neoplasms↗
PubMed1995

Chromosome abnormalities in bilateral breast carcinomas. Cytogenetic evaluation of the clonal origin of multiple primary tumors.

BACKGROUND: Although acquired somatic mutations presumably are crucial in carcinogenesis, nothing is known about the chromosome aberrations of bilateral breast carcinomas. METHODS: Eighteen specimens from 16 bilateral carcinomas were analyzed cytogenetically. The banding analysis was supplemented with fluorescence in situ hybridization with painting probes. RESULTS: In two cases, the finding of the same clonal abnormalities in samples from both breasts indicated that the bilaterality had arisen through a metastatic process. In the remaining cases, the absence of similarities between the two sides indicated an independent origin of the two carcinomas. Also, in multifocal lesions within the same breast, examples were found both of karyotypically related and unrelated clones. Altogether, multiple clones without similarities were detected in nine specimens, sometimes together with other, karyotypically related clones. There was no indication that bilateral carcinomas of the breast are cytogenetically different from unilateral ones. The following chromosomal abnormalities were recurrent: der(1;16)(q10;p10), del(1)(q11-n12), del(1)(q42), and del(3)(p12-n13p14-n21). CONCLUSIONS: Bilateral breast carcinomas have the same cytogenetic aberrations, including evidence of polyclonality, as unilateral carcinomas. The majority apparently arise independently, but some result from a metastasis from one breast to the other. In this sense, bilateral breast carcinomas are similar to multifocal breast cancer in general, of which bilateral tumors may represent a special case.

Aged↗
PubMed1995

Chromosome abnormalities in benign hyperproliferative disorders of epithelial and stromal breast tissue.

Cytogenetic analysis of short-term cultures from 15 cases of benign proliferative breast disease (PBD), 10 diffuse PBD and 5 papillomas, and 15 fibroadenomas of the breast revealed clonal chromosome abnormalities in 7 diffuse PBD lesions, 4 papillomas and 5 fibroadenomas. The remaining 14 cases had a normal female chromosome complement. Cytogenetically unrelated abnormal clones were seen in 4 fibroadenomas and 2 PBDs. A single abnormal clone was found in 9 PBDs and 1 fibroadenoma. Three clonal abnormalities were seen as recurrent changes in 6 cases, namely interstitial deletions of 3p with 3p 12-14 as the minimally common deleted segment (in 1 papilloma, 1 diffuse PBD with atypia and 1 mixed-pattern lesion with both papilloma and atypical diffuse PBD features), r(9)(p24q34) (in 1 diffuse PBD and 1 fibroadenoma), and del(1)(q12)(again in 1 diffuse PBD and 1 fibroadenoma). Intriguingly, 6 of the 16 abnormal cases had chromosome changes that have been seen repeatedly as primary abnormalities in breast carcinomas: der(16)t(1;16)(q10;p10), del(3)(p12p14), and del(1)(q12). We conclude that some of the chromosome anomalies frequently found in breast carcinomas are also present in PBD and fibroadenomas. These aberrations may be accepted as early, neoplasia-relevant mutations. However, they do not seem to be sufficient by themselves to unleash a malignant process.

Breast↗
PubMed1995

DNA aneuploidy in early breast cancer.

High-resolution flow cytometric (FCM) DNA analysis was performed on 148 unfixed, frozen tissue samples from four groups of early breast cancers: invasive carcinomas (ICs) with predominance of carcinoma in situ (DCIS) (group I), small clinical cancers < or = 15 mm (group II), node-negative, clinical cancers (group III) and small screening-detected cancers < or = 15 mm (group IV). The median tumour size was 12 mm. The aim of the study was to support, with a larger sample, our recent findings with respect to DNA ploidy pattern in the selected group of ICs with predominance of DCIS (group I). Similar results to this group were found for both the small clinical cancers and the node-negative cancers, with respect to frequency of DNA aneuploidy (79% and 90%), DNA index (DI) distribution, intratumoral DNA heterogeneity and S-phase fraction. A high frequency of DNA hyperdiploid clones was found, in particular related to highly differentiated tumours. A significant difference was found compared with the screening-detected cancers, which were characterised by a much lower frequency of DNA aneuploid samples (49%) and may represent a biologically specific group of low-malignant, slowly growing tumours. Associations were shown between histological grade and DI subclasses, and between lymph node status and DNA diploidy/aneuploidy, whereas DI was not correlated with tumour size. The DNA ploidy findings in this series of early cancers are concordant to our own results from preinvasive lesions as well as those reported from series of more advanced cancers.

Adult↗
PubMed1994

Karyotypic changes in phyllodes tumors of the breast.

Cytogenetic analysis of short-term cultures of five phyllodes tumors of the breast-classified as benign (one tumor), borderline malignant (two tumors removed from the same breast in 1991 and 1993), and malignant (two tumors)--revealed clonal changes with simple structural abnormalities in the benign tumor, the borderline malignant tumors, and one malignant tumor in which benign areas and areas of borderline malignancy were also present. In contrast, the malignant tumor without admixed borderline malignant or benign areas had a complex karyotype. The karyotype of the benign phyllodes tumor was 46,XX,del(12)(p11p12)/46,XX,t(8;18)(p11;p11)/46,XX. The first borderline malignant phyllodes tumor had t(3;20)(p21;q13) as the sole abnormality. When the tumor recurred, this was no longer the only clone detected and the tumor karyotype was now 46,XX,t(3;20)(p21;q13)/46,XX,t(9;10)(p22;q22)/46,XX,t(1;8) (p34;q24)/46,XX,del(11)(q22-23)/46,XX. The malignant/borderline malignant/benign tumor had t(1;6)(p34;p22) as the sole clonal abnormality. Finally, the karyotype of the malignant phyllodes tumor which contained no benign or borderline malignant areas was 42,XX,der(1)t(1;4)(q21;q21),der(3)t(3;17)(q29;q21), -4,i(8)(q10), -10, -13,i(13)(q10),der(14)t(1;14)(q21;p11),der(14)t(4;14) (p12;p11), -17/80-90,idemx2, +del(1)(q12), +i(1)(p10), +dic(5;5)(p14;p14), +i(6)(p10), +del(7)(p11), +dup(7)(q11q36), +i(15)(q10),inc/46,XX. The findings indicate some cytogenetic similarities between benign/borderline malignant phyllodes tumors and fibroadenomas of the breast, presumably reflecting similar pathogenetic mechanisms in the two types of mixed-lineage tumors.

Aged↗
PubMed1994

Chromosome abnormalities in adenolipomas of the breast: karyotypic evidence that the mesenchymal component constitutes the neoplastic parenchyma.

Cytogenetic analysis of adenolipomas of the breast, a tumor type that has not been chromosomally characterized before, revealed the karyotypes 47,XX, +del(1)(p22) in one tumor and 46,XX, t(12;16)(q15;q24) in the other. Breast adenolipomas thus seem to be karyotypically identical to sporadic lipomas in other locations: rearrangements of 12q13-15 are the most common cytogenetic aberrations in lipomas, and also breaks in and around 1p22 have been reported in such tumors. The similarity with lipoma could be documented further in case 2, in which epithelial and mesenchymal cells were cultured separately; the t(12;16) was present in the latter but not in the former. This is evidence that the connective tissue is the neoplastic parenchyma in adenolipomas of the breast, whereas the glandular elements show concomitant but nonneoplastic proliferation.

Adenoma↗
PubMed1994

Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci.

Cytogenetic analysis was performed on short-term cell cultures of two foci (A and B) from each of three multifocal breast carcinomas. In case I, four clones (three related and one unrelated) were detected in sample A. In sample B, two of the three related clones and the unrelated clone seen in A were found, as was also a third subclone showing a pattern of clonal evolution slightly different from that detected in A. In cases II and III, multiple cytogenetically unrelated clones were found in A and B, with only one clone being shared by both foci in each case. Our finding of cytogenetic similarities between macroscopically distinct tumour lesions indicates that the multifocality reflects intramammary tumour spread rather than the synchronous emergence of pathogenetically independent carcinomas within the same breast. On the other hand, the detection of karyotypic heterogeneity in the form of cytogenetically unrelated clones in all foci suggests that human breast carcinoma may be polyclonal. This polyclonality may be part of the explanation for the cellular heterogeneity commonly seen at the phenotypic level in breast cancer.

Aged↗
PubMed1993

[The duct ectasia syndrome. A prospective clinical study of patients with breast diseases].

Mammary duct ectasia is a benign condition of the mammary gland histopathologically characterized by inflammatory changes in the collecting ducts. A prospective clinical and histopathological study was done of 316 consecutive patients with surgical mammary diseases. The syndrome of mammary duct ectasia (DES) was found in 42 patients (13%). The mean age was 44 years and 81% of the patients were pre- or menopausal. Forty-eight percent of the patients had a history of previous benign breast lesions and abnormality associated with lactation was also frequently represented in the history. Major symptoms were tumour formation, localised in the subareolar region in more than half of the cases, subareolar abscess and nipple discharge. Minor symptoms were mastalgia, mammary fistula, nipple retraction, general symptoms and enlarged axillary lymph nodes. Treatment for an abscess in DES seems to fail more often if only incision and drainage are performed. Excision of the entire focus and corresponding duct may prove to be better.

Adolescent↗
PubMed1993

[The duct ectasia syndrome--an overlooked disease entity].

Mammary duct ectasia is a benign disease of the mammary gland, characterized by a frequently long history of tumour formation, nipple discharge, nipple retraction and mastalgia. Non-puerperal mammary abscess, which may be the presenting symptom, is also part of the syndrome. Diagnosis can often be made on the basis of the history and the clinical findings of nipple discharge, nipple retraction, tenderness on palpation, fistula formation and subareolar tumour/abscess formation. Mammography may guide diagnosis. Breast cancer is the most important differential diagnosis. If the clinical picture resembles cancer, it is necessary to perform diagnostic biopsy. Causal therapy of mammary duct ectasia is not available. Until now excision of the central mammary tissue and larger ducts has been used as treatment for the clinical manifestations of abscess, fistula and nipple discharge, apparently with good results.

Breast↗
PubMed1993

Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinomas and atypical lesions of the breast, 88 women, comprising 69 patients with lobular carcinoma in situ (LCIS) and 19 patients with combined lobular and ductal carcinoma in situ (LCIS + DCIS), were accrued from 1982 through 1987. All cases were treated with excision only. Within a median follow-up time of 61 months, a recurrence rate of 17% (15 cases) was found, excluding nine cases of refinding of LCIS. No contralateral recurrences occurred. The recurrences were in eight cases invasive carcinomas (IC), in six cases LCIS + DCIS, and in one case DCIS alone. The recurrence rates among cases of LCIS and of LCIS + DCIS were not significantly different. The histopathological review included an estimate of the number of lobules with LCIS and nuclear size, both of which were significantly related to recurrence. The risk of developing IC was calculated to be increased by a factor 11 as compared with the reference population.

Adult↗
PubMed1993

Needle biopsy of breast cancer. Appearance of tumour cells along the needle track.

Appearance of tumour cells along the needle track in patients with breast cancer diagnosed by SURECUT needle biopsy is found in two out of 47 consecutive cases. It is not known whether these cells are early implantation metastases or are harmless. To avoid any unnecessary risk to the patients, we recommend that needle biopsy is so performed, that it is possible to remove the track during the definite surgical procedure, and that penetration into the muscles of the thoracic wall during the biopsy procedure is avoided.

Biopsy, Needle↗
PubMed1992

[Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status].

The present study evaluates the extent of axillary dissection as part of the primary surgical treatment of operable breast cancer. Data are from the period January 1979 to August 1990 and were collected prospectively as part of the Danish Breast Cancer Cooperative Group protocols for low-risk mammary carcinoma. The series consists of 6774 breast cancer patients aged 69 years or younger. The number of axillary lymph nodes removed was related to the frequency of ipsilateral axillary recurrence, recurrence-free survival, and overall survival after a median of five years follow-up, respectively. The recurrence-free survival and overall survival rate were directly related to the number of axillary lymph nodes removed. The difference in outcome is believed to be caused by false-negative classification of axillary-positive high-risk patients in groups of patients where only a few axillary lymph nodes were removed.

Adult↗
PubMed1992

Ductal carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinoma of the breast, 112 women with ductal carcinoma in situ, treated with excision only, were registered from 1982 to 1987. Within a median follow-up of 53 months, a crude recurrence rate of 22% (25 cases) was found, of which five cases recurred as invasive carcinomas and 20 cases as in situ carcinomas. The histopathologic review included a single-parameter analysis of histological growth pattern, size of lesion, nuclear size, presence of comedonecrosis, and subhistologic type. A strong interrelationship was found for histological growth pattern, nuclear size, and comedonecrosis. These parameters were also significantly related to recurrence. Cases that had clinical symptoms had a high recurrence rate as compared with cases that were discovered by mammography only or incidentally.

Adult↗
PubMed1992

Foetal antigen 2 (FA2) in relation to wound healing and fibroblast proliferation.

During wound healing of human skin the deposition of foetal antigen 2 (FA2) and basement membrane (BM) components collagen type IV and collagen VII was followed. FA2 appeared on day 8 in the cytoplasm of proliferating fibroblasts and around newly formed blood vessels. As granulation tissue was formed, FA2 was seen diffusely in the loose matrix and in proliferating fibroblasts. Re-establishment of FA2 as a broad diffuse band along the BM at the dermo-epidermal junction was seen on day 22. In contrast, type IV and VII collagen were found along the BM and in the basal cells of the newly formed epithelium and a continuous linear BM distribution of these two components were re-established by days 12 and 14, respectively. The molecular weight (Mr) analysis of FA2, isolated from human skin fibroblast culture supernatants using SDS-PAGE, revealed a Mr of 27 kDa, corresponding to that of FA2 isolated from amniotic fluid. The presence of FA2 in proliferating fibroblasts and diffusely in the newly formed matrix of granulation tissue, as well as its late appearance at the BM after this had become established, suggests that FA2 takes part in connective tissue metabolism and perhaps tissue morphogenesis.

Amniotic Fluid↗
PubMed1992

Foetal antigen 2 (FA2) in the stromal reaction induced by breast carcinoma.

An indirect immunoperoxidase technique was used to examine the distribution of foetal antigen 2 (FA2), a recently described basement membrane (BM)-associated antigen, in invasive breast carcinoma (n = 34), fibroadenoma (n = 5) and normal breast tissue (n = 5), and to compare its distribution with that of laminin and collagen type IV. In normal breast tissue, FA2 was detected in the intralobular stroma as a broad band around acini and ducts, but was not present in the interlobular stroma. In areas of carcinoma in situ, FA2 was present diffusely around and in close contact with the glandular elements, the staining being more intense than that found around normal glandular structures. Two distinct patterns of FA2 distribution were found in adenocarcinomas of the breast. In the fibroblast reaction type, fibroblast staining dominated, whilst in the stromal reaction type, intense and extensive staining of the surrounding stroma dominated. Significant correlation was found between the degree of fibroblast activity and the degree of anaplasia (p = 0.005). FA2 extracted from breast carcinoma tissue was shown to be immunologically identical to FA2 fractions extracted from second trimester amniotic fluid (AF). The Mr of FA2 isolated from AF was estimated to be 26 kD, whereas the Mr of FA2 extracted from breast carcinoma tissue was slightly higher. The apparent Mr under reducing conditions were higher and three bands ranging from 26 to 29 kD were seen. FA2 was found to be immunologically distinct from collagen types I, III and IV, laminin, fibronectin and fibrinogen. The increased production and widespread distribution of FA2 in breast carcinomas suggest that FA2 is involved in the stromal changes which occur in response to tumour growth and/or invasion.

Adenocarcinoma↗
PubMed1992

Primary non-Hodgkin's lymphoma of the breast (PLB): a clinicopathological study of seven cases.

Seven cases of PLB in females were reviewed. Six cases involved the breast alone (stage 1E), whereas one case also involved the ipsilateral lymph nodes (stage 2E). None had B symptoms. The age range was 37-70 years (mean 52 years). The clinical course was indistinguishable from that of breast carcinomas, though the tumors were relatively large and the duration of symptoms was relatively short. Histologically, all cases were non-Hodgkin's B-cell lymphomas, comprising five cases of diffuse centroblastic type, one case of diffuse centroblastic-centrocytoid type and one case of follicular centroblastic-centrocytic type, according to the updated Kiel classification, corresponding to six cases of the diffuse large cell type and one case of the follicular mixed, small cleaved and large cell type, according to the modified International Working Formulation (IWF). None of the cases was a lymphoma of mucosa-associated lymphoid tissue (MALT). The mammary glandular tissue outside the tumor showed ductectasia in four cases. Changes resembling fibrous disease of the breast were seen in four cases, too. The inflammatory infiltration in all these cases was mainly composed of T cells. At the time of diagnosis, all patients were receiving cytoreductive treatment. The mean follow-up time was 34 months (range 5-79 months). At present, six of the patients are alive and well.

Adult↗