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'Revertant' DCIS in human axillary breast carcinoma metastases
S H Barsky1, S A Doberneck, M D Sternlicht
1Department of Pathology, UCLA School of Medicine 90024, USA.
Abstract:
Recent experimental evidence obtained in Scid mice has suggested that the metastatic process is in large part epigenetically regulated and undergoes partial reversion once the metastatic process is completed: the metastatic colonies become more engaged in the process of growing in situ than actively metastasizing. Based on this experimental evidence, examples were sought of metastatic human cancers where similar reversion to an in situ growth state was occurring. Review of 200 cases of metastatic human breast cancer revealed a 21 per cent incidence of reversion to a ductal carcinoma in situ (DCIS) growth pattern within axillary nodal metastases. The revertant DCIS areas were characterized by an intact and circumferential basement membrane, as demonstrated by extracellular laminin and type IV collagen immunoreactivity. These revertant DCIS areas could be distinguished from primary DCIS, however, by the absence of surrounding myoepithelial cells in the former, identified in the latter by their positive maspin, S-100, and smooth muscle actin immunoreactivity. The pattern of revertant DCIS, poorly differentiated (comedo) (13 per cent), intermediate (non-comedo) (6 per cent), or well-differentiated (non-comedo) (2%), exhibited complete 100 per cent concordance with the primary DCIS pattern. The concordance of histological patterns held true for even the subtypes of DCIS determined by architectural pattern, such as the micropapillary or cribriform subtypes. Nuclear size by digital image analysis and Her-2/neu, p53, and Ki-67 status in the revertant DCIS also exhibited complete concordance with the primary DCIS counterparts. Cases exhibiting a revertant DCIS pattern tended to be ER-negative/EGFR-positive and exhibited significant nodal involvement (mean number, 9; mean area, 90 per cent) compared with cases lacking a revertant pattern (mean number, 4; mean area, 15 per cent) (P < 0.01) These findings suggest that reversion of the metastatic phenotype may also be occurring within autochthonous human metastasis.
Insights
Metastatic breast cancer can revert to a non-invasive ductal carcinoma in situ (DCIS) growth pattern within lymph nodes. This reversion shows distinct characteristics and may indicate epigenetic regulation of metastasis.
Area of Science:
- Oncology
- Cancer Biology
- Epigenetics
Background:
- Experimental evidence in mice suggests epigenetic regulation of metastasis with partial reversion.
- Metastatic colonies may shift from active spreading to in situ growth post-colonization.
Purpose of the Study:
- To investigate the occurrence of metastatic reversion to ductal carcinoma in situ (DCIS) in human breast cancer.
- To characterize the histological and molecular features of revertant DCIS in nodal metastases.
Main Methods:
- Review of 200 cases of metastatic human breast cancer.
- Immunohistochemical analysis for basement membrane components (laminin, type IV collagen) and myoepithelial markers (maspin, S-100, smooth muscle actin).
- Digital image analysis for nuclear size and assessment of Her-2/neu, p53, Ki-67, ER, and EGFR status.
Main Results:
- A 21% incidence of reversion to DCIS pattern was observed in axillary nodal metastases.
- Revertant DCIS areas showed intact basement membranes but lacked myoepithelial cells, distinguishing them from primary DCIS.
- Histological patterns, subtypes, nuclear size, and molecular markers (Her-2/neu, p53, Ki-67) of revertant DCIS were highly concordant with primary DCIS.
- Revertant DCIS cases were associated with ER-negative/EGFR-positive status and significantly higher nodal involvement.
Conclusions:
- The findings suggest that reversion of the metastatic phenotype occurs in human breast cancer, specifically to a DCIS-like state within metastases.
- This reversion phenomenon may be epigenetically regulated, mirroring observations in experimental models.
- The presence of revertant DCIS is linked to more extensive nodal disease and specific receptor expression patterns.
