Abstract
Although breast carcinomas are considered to originate from glandular epithelial cells, some exhibit 'squamoid features', comprising stratification with a gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on microscopy. In parallel with a histological review of squamoid features, we immunohistochemically investigated the expression of involucrin, a marker of terminal squamous differentiation, in 223 breast carcinomas with one to three regional nodal metastases but no distant metastases and analysed their association with other clinicopathological parameters to explore their clinical and biological implications. Squamoid features and involucrin expression, detected in 22% and 27% of cases respectively, correlated with each other and were associated with high-grade atypia, a solid-nest pattern, cancer cell necrosis on histology and negative oestrogen receptor status. The incidence of regional recurrences was higher in patients with involucrin expression, whereas bone metastases were less frequent in groups with squamoid features or with diffuse (> or = 10%) involucrin expression. Both squamoid features and involucrin expression, which were considered to be derived either from differentiation into keratinocytes or from some kind of cellular degeneration caused by high turnover rate, are suggested to influence the biological behaviour of breast cancer cells in vivo, and they may be effective in predicting the most likely recurrence sites.
Highlights
To reveal clinical and biological implications of squamoid features in breast cancer cells, we reviewed haematoxylin-eosin-stained tissue sections to identify stratification of cancer cell nests and immunohistochemically investigated the expression of involucrin in 223 primary breast cancers with a nearly identical degree of local spread
Squamoid features were observed in both individual solid nests and in cells forming strands that are involved in the fibrous or collagenous stroma at the tumour centre (Figure lA-D)
Involucrin expression was mostly detected in solid nests of cancer cells showing a low nuclear/cytoplasmic ratio, eosinophilic or glassy cytoplasm, and clear intercellular borders (Figure 2)
Summary
To avoid any effect of the degree of local tumour spread on the type of recurrence site, we selected breast cancer patients with metastases in one to three axillary lymph nodes. Data were acquired from individual medical charts for tumour size on palpation, the number of regional metastases, oestrogen receptor (OR) status, overall and disease-free survival after mastectomy, cause of death and the first and any subsequent recurrence sites detected clinically and/or by imaging during follow-up. The recurrence sites were categorized into two: (1) regional recurrences, including local recurrence in the skin and/or chest wall and metastasis to the ipsilateral supraclavicular or cervical lymph nodes; and (2) distant metastases, composed of five subclassifications - lung and/or pleura, bone, liver, brain and others
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