Are acinic cell carcinomas of the breast and salivary glands distinct diseases?

Abstract

Aims Acinic cell carcinomas (AcCC) of the breast have been reported to constitute the breast counterpart of salivary gland AcCCs, based on the similarities of their histological and immunohistochemical features. Breast AcCC is a vanishingly rare form of triple-negative breast cancer (TNBC). Recent studies have demonstrated that in TNBCs, the two driver genes most frequently mutated are TP53 (82%) and PIK3CA (10%). We sought to define whether breast AcCCs would harbour TP53 and PIK3CA somatic mutations, and if so, whether these would be present in salivary gland AcCCs. Methods and results Sanger sequencing of the entire coding region of TP53 and of PIK3CA hotspot mutation sites of 10 breast and 20 salivary gland microdissected AcCCs revealed eight TP53 (80%) and one PIK3CA (10%) somatic mutations in breast AcCCs. No somatic mutations affecting these genes were found in the 20 salivary gland AcCCs analysed. Conclusions Our findings demonstrate that breast AcCCs display TP53 and PIK3CA mutations at frequencies similar to those of common types of TNBCs, whereas these genes appear not to be altered in salivary gland AcCCs, suggesting that despite their similar histological appearances, AcCCs of the breast and salivary glands probably constitute unrelated diseases.

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

“…The presence of a TP53 mutation in the molecular analysis of the first case described in this article is in keeping with the findings of Ripamonti et al [19], who reported the presence of a TP53 mutation in a breast AcCC that occurred in a BRCA1 mutation carrier, and Piscuoglio et al [27], who recently described TP53 mutations in 80% (8/10) of breast AcCCs tested. TP53 mutation was found in 37% of all breast carcinomas tested in The Cancer Genome Atlas breast carcinoma study [30] and is the most common mutation in breast cancer.…”

“…There have been 47 cases of breast AcCC reported in the English language literature, including the 2 new cases reported in this article [1,4,7–27]. A detailed morphologic description was provided in 31 of these cases [1,4,7–25].…”

“…Of the 47 breast AcCC cases reported, 15 patients (32%) had an associated IDC NOS; of these, 10 had a solid, poorly differentiated carcinoma, 2 had a well-differentiated tubular/microglandular carcinoma, 1 had a moderately differentiated carcinoma, whereas 1 metaplastic carcinoma has also been reported [4,8,11,23,27]. Tumor grade was not detailed in the remaining cases.…”

The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis‐generating study

“…Histologic and immunohistochemical details of the cases included in this study are reported elsewhere [24]. All cases were reviewed by four of the authors (ZH, EAR, IOE and JSR-F), and classified as pure ACCs (n=2) and mixed ACCs (n=6; Table 1).…”

“…A recent case report demonstrated that breast ACCs may develop in the context of BRCA1 germline mutation carriers; genetic analysis of one such case revealed loss of heterozygosity (LOH) of the BRCA1 locus and the presence of a TP53 somatic mutation, akin to other types of BRCA1 -related breast cancers [23]. Our group has recently demonstrated by Sanger sequencing analysis that, like common types of TNBC, TP53 mutations are found in up to 80% of breast ACCs [24]. …”