DNA ploidy of primary breast cancer and local recurrence after breast-conserving therapy

Abstract

Summary The value of DNA-flow cytometry and clinico-pathological prognostic factors for the prediction of local recurrences after breast-conserving therapy (BCT) were evaluated in a retrospective study. Thirty-one patients with a local recurrence were compared with 31 matched patients without a local recurrence. Morphology and DNA-indices of the local recurrences and their corresponding primary tumours were compared. Ductal carcinoma in situ was present significantly more often in the group with a primary recurring tumour, than in the matched group (P <0.001), and the same holds for lobular carcinoma (n = 5). Half of the tumours that recurred had macroscopically positive surgical margins compared to about one-fourth of the matched group. Fifty-six per cent of the DNA-aneuploid stemlines in cases with local recurrence were present in the corresponding primary tumour as well (confidence limits 45%-75%), an indication that the majority of local recurrences are true recurrences and not independently developed tumours. The lack of similarlity of DNA stemlines between some primary DNA-aneuploid tumours and their local recurrences indicates that these tumours had developed independently. The percentage of DNA-aneuploid cases in the group with local recurrence (89%) did not differ significantly from that in the matched group (70%). However, the findings suggest a selective recurrence of DNA-diploid stemlines. This might indicate increased resistance of DNAdiploid tumour cells to radiotherapy as compared with the resistance level in DNA-aneuploid cells.

Flow Cytometry Dna Analysis and Prediction of Loco-Regional Recurrences After Mastectomy in Breast Cancer

“…Neither tumor size, nor ploidy status, level of SPF, or ER content was an independent prognostic variable concerning LRR. Our findings are consistent with a report by Beerman et al (21) who, in a study of patients who had undergone breast saving treatment, found no significant difference in ploidy status between patients with recurrence in the treated breast and those without (21).…”

Allelotype analysis of flow-sorted breast cancer cells demonstrates genetically related diploid and aneuploid subpopulations in primary tumors and lymph node metastases

“…Here we present unequivocal molecular genetic evidence for a clonal relationship between subpopulations of tumor cells derived from primary breast tumors and their lymph node metastases. Our results support previously reported evidence for intratumor DNA index heterogeneity in breast carcinomas and similar metastatic capacity for both diploid and aneuploid clones (Beerman et al, 1991a, 1991b; Bonsing et al, 1993a; Schvimer et al, 1995; Symmans et al, 1995; Visscher et al, 1995). The continuous coexistence in primary tumors of diploid clones with limited AI and the genetically related but more advanced aneuploid clones suggests that clonal evolution does not necessarily equal clonal succession (Heim et al, 1988; Dutrillaux et al, 1991; Cornelisse et al, 1994; Shackney et al, 1995; Lengauer et al, 1998).…”

“…Many chromosomes at varying frequencies and combinations have been shown, by different approaches (e.g., karyotype analysis, CGH, allelotyping), to be involved in breast carcinoma development, suggesting multiple genetic routes (van de Vijver, 1993; Radford et al, 1995; Fujii et al, 1996a; Kuukasjarvi et al, 1997). Dissection of these routes is hampered by extensive intratumor heterogeneity at the genetic level (Beerman et al, 1991a, 1991b; Bonsing et al, 1993a; Fiegl et al, 1995; Schvimer et al, 1995; Symmans et al, 1995; Teixeira et al, 1995; Visscher et al, 1995; Simpson et al, 1996). Chromosome banding analysis (Teixeira et al, 1994, 1995, 1996; Pandis et al, 1998) and fluorescence in situ hybridisation studies (Balazs et al, 1995; Fiegl et al, 1995; Leuschner et al, 1996; Simpson et al, 1996) demonstrated multiple, clonal subpopulations within the majority of breast carcinomas.…”

Cuantificación de ADN y CK18 por citometría de flujo multiparamétrica en el cáncer de mama inicial en el tumor primario y ganglios centinelas. Valor pronóstico a largo plazo

“…Como ya se ha comentado, en este estudio detectamos un alto grado de heterogeneidad tanto en lo referente a la ploidía del ADN como en la expresión de CK18 en el tumor primario. Meyer (263), Beerman (264), Prey (265), Fuhr (266) y otros autores (267-270) también han informado de la existencia de heterogeneidad cuando se estudian diferentes muestras de tumor, lo que puede tener importancia desde el punto de vista del pronóstico (268,271). Aunque la heterogeneidad celular es mayor en los tumores más grandes, varios autores afirman que ésta es una característica intrínseca del cáncer de mama, y que está presente incluso en tumores de pequeño tamaño, por lo que se propone un muestreo múltiple de diversas zonas del tumor a la hora de analizarlo, para así tener una muestra más representativa de todas las poblaciones celulares que lo forman (265, 266).…”

“…En un 33.6% (42 tumores) se encontraron 2 clones, 3 clones en el 9.6% (12 tumores), 4 en el 2.4% (3 tumores) y 5 clones en el 3.2% (4 tumores). Como ya se ha comentado, esta gran heterogeneidad tumoral está en línea con otras publicaciones (263,266,271) aunque en contra de otras (265, 267), si bien estas diferencias estarán basadas, en gran medida, en las estrategias usadas para la detección de aneuploidía, pues clones aneuploides minoritarios o con un índice de ADN (IADN) próximo a 1.00, pueden pasar desapercibidos si el análisis es uniparamétrico o los coeficientes de variación son elevados.…”