Molecular abnormalities associated with secretory carcinomas of the breast

Anirban Maitra, Fattaneh A. Tavassoli, Jorge Albores-Saavedra, Carmen Behrens, Ignacio I. Wistuba, David Bryant, Arthur G. Weinberg, Beverly B. Rogers, M. Hossein Saboorian, Adi F. Gazdar

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Secretory carcinomas (SCAs) represent a unique histological variant of invasive breast carcinomas, occurring predominantly in patients younger than 30 years of age. Data from limited series have shown SCAs to have a favorable prognosis in patients younger than 20 years of age, whereas the clinical course tends to parallel the more common infiltrating ductal carcinomas (IDCs) in patients older than 20 years. There are no reports on the molecular abnormalities associated with this unusual tumor. Microdissected archival formalin-fixed tissue from 10 SCAs collected from 2 institutions were used to determine the frequencies of allelic loss at 13 chromosomal regions with 19 microsatellite markers, using multiplex polymerase chain reaction (PCR)-based techniques. The results of loss of heterozygosity (LOH) and microsatellite alterations (MAs) analyses were compared with 20 cases of IDCs. P53 gene mutation analysis was also performed on the 10 SCAs using single-strand conformation polymorphism (SSCP) analysis, followed by sequencing of abnormal bands. LOH at multiple regions of chromosome 3p were the most common abnormality in both SCAs (55%) and IDCs (50%), followed by LOH at 17q21 (BRCA1 locus), 13q14 (retinoblastoma gene locus), and 8p21- 23. No significant differences were seen in the frequencies of LOH at any chromosomal region except for 17p13 (p53 gene locus), where allelic losses were absent in SCAs, but evident in 46% of IDCs (P < .05). The 2 histological entities were similar in the fractional regional loss (FRL) index (0.26 v 0.24), fractional allelic loss (FAL) index (0.23 v 0.27), as well as in the frequency of MAs (0.015 v 0.005), P > .05. P53 gene missense mutation (G:C::A:T) was detected in 1 of 10 (10%) SCAs. Based on the considerable similarities in the molecular abnormalities associated with both tumors, the formation of secondary lumina in both the in situ and the invasive components, as well as suggestions from limited series that the clinical behavior in adult patients parallels that of IDCs, SCA most likely reflects a secretory variant of IDCs.

Original languageEnglish (US)
Pages (from-to)1435-1440
Number of pages6
JournalHuman Pathology
Volume30
Issue number12
StatePublished - 1999

Fingerprint

Ductal Carcinoma
Loss of Heterozygosity
Carcinoma
p53 Genes
Microsatellite Repeats
Retinoblastoma Genes
Secretory breast carcinoma
Multiplex Polymerase Chain Reaction
Missense Mutation
Formaldehyde
Neoplasms
Chromosomes
Breast Neoplasms
Mutation

Keywords

  • Infiltrating ductal carcinomas
  • Loss of heterozygosity
  • p53 mutation
  • Secretory carcinomas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Maitra, A., Tavassoli, F. A., Albores-Saavedra, J., Behrens, C., Wistuba, I. I., Bryant, D., ... Gazdar, A. F. (1999). Molecular abnormalities associated with secretory carcinomas of the breast. Human Pathology, 30(12), 1435-1440.

Molecular abnormalities associated with secretory carcinomas of the breast. / Maitra, Anirban; Tavassoli, Fattaneh A.; Albores-Saavedra, Jorge; Behrens, Carmen; Wistuba, Ignacio I.; Bryant, David; Weinberg, Arthur G.; Rogers, Beverly B.; Saboorian, M. Hossein; Gazdar, Adi F.

In: Human Pathology, Vol. 30, No. 12, 1999, p. 1435-1440.

Research output: Contribution to journalArticle

Maitra, A, Tavassoli, FA, Albores-Saavedra, J, Behrens, C, Wistuba, II, Bryant, D, Weinberg, AG, Rogers, BB, Saboorian, MH & Gazdar, AF 1999, 'Molecular abnormalities associated with secretory carcinomas of the breast', Human Pathology, vol. 30, no. 12, pp. 1435-1440.
Maitra A, Tavassoli FA, Albores-Saavedra J, Behrens C, Wistuba II, Bryant D et al. Molecular abnormalities associated with secretory carcinomas of the breast. Human Pathology. 1999;30(12):1435-1440.
Maitra, Anirban ; Tavassoli, Fattaneh A. ; Albores-Saavedra, Jorge ; Behrens, Carmen ; Wistuba, Ignacio I. ; Bryant, David ; Weinberg, Arthur G. ; Rogers, Beverly B. ; Saboorian, M. Hossein ; Gazdar, Adi F. / Molecular abnormalities associated with secretory carcinomas of the breast. In: Human Pathology. 1999 ; Vol. 30, No. 12. pp. 1435-1440.
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abstract = "Secretory carcinomas (SCAs) represent a unique histological variant of invasive breast carcinomas, occurring predominantly in patients younger than 30 years of age. Data from limited series have shown SCAs to have a favorable prognosis in patients younger than 20 years of age, whereas the clinical course tends to parallel the more common infiltrating ductal carcinomas (IDCs) in patients older than 20 years. There are no reports on the molecular abnormalities associated with this unusual tumor. Microdissected archival formalin-fixed tissue from 10 SCAs collected from 2 institutions were used to determine the frequencies of allelic loss at 13 chromosomal regions with 19 microsatellite markers, using multiplex polymerase chain reaction (PCR)-based techniques. The results of loss of heterozygosity (LOH) and microsatellite alterations (MAs) analyses were compared with 20 cases of IDCs. P53 gene mutation analysis was also performed on the 10 SCAs using single-strand conformation polymorphism (SSCP) analysis, followed by sequencing of abnormal bands. LOH at multiple regions of chromosome 3p were the most common abnormality in both SCAs (55{\%}) and IDCs (50{\%}), followed by LOH at 17q21 (BRCA1 locus), 13q14 (retinoblastoma gene locus), and 8p21- 23. No significant differences were seen in the frequencies of LOH at any chromosomal region except for 17p13 (p53 gene locus), where allelic losses were absent in SCAs, but evident in 46{\%} of IDCs (P < .05). The 2 histological entities were similar in the fractional regional loss (FRL) index (0.26 v 0.24), fractional allelic loss (FAL) index (0.23 v 0.27), as well as in the frequency of MAs (0.015 v 0.005), P > .05. P53 gene missense mutation (G:C::A:T) was detected in 1 of 10 (10{\%}) SCAs. Based on the considerable similarities in the molecular abnormalities associated with both tumors, the formation of secondary lumina in both the in situ and the invasive components, as well as suggestions from limited series that the clinical behavior in adult patients parallels that of IDCs, SCA most likely reflects a secretory variant of IDCs.",
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AU - Wistuba, Ignacio I.

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AU - Saboorian, M. Hossein

AU - Gazdar, Adi F.

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