Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: a clinicopathological study

Abstract

Background: Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6.

Methods: Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters.

Results: The series consisted of invasive ductal carcinoma (n = 9), invasive lobular carcinoma (n = 9), and mucinous carcinoma (n = 4) cases. The SRC population accounted for 8-81 % of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n = 12) and low (n = 10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n = 11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n = 11; p = 0.01, p = 0.002, p = 0.008, and p = 0.02, respectively). The CM group (n = 7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67 indices than the LC group (n = 15; p = 0.04, p = 0.001, p = 0.006, and p = 0.03, respectively). The expression levels of MUC2, MUC4, MUC5AC, and MUC6 showed no clinicopathological significance. Two patients with low MUC1 expression and CM patterns had tumor recurrence, resulting in death, while all the other patients survived without recurrence.

Conclusion: Our results demonstrate that in breast cancers containing SRCs, low MUC1 expression and/or its CM subcellular localization patterns are associated with unfavorable clinicopathological factors. The utility of MUC1 expression as a prognostic marker remains to be verified in future studies.

Keywords: Breast cancer; Mucin; Signet ring cells.

Fig. 1

Signet ring cells (SRCs) in invasive ductal carcinoma of no special type (a and b), invasive lobular carcinoma (c), and mucinous carcinoma (d). The intracytoplasmic lumen (ICL) type of SRCs is represented by discrete vacuoles with targetoid appearance (a and c), whereas the non-ICL type has abundant intracytoplasmic mucin dislodging the nucleus to one end of the cells, as seen in gastric carcinoma (b and d). Hematoxylin and eosin staining (a–d). Original magnification × 600 (a–d)

Fig. 2

Immunohistochemical expression of MUC1 (a–f). In normal breast tissue, MUC1 is constitutively expressed in the apical and luminal sites of the ductal epithelia with weak cytoplasmic positivity (a). MUC1 was notably expressed in invasive ductal carcinoma (b and c) and invasive lobular carcinoma (d and e) either in a luminal and cytoplasmic pattern (b and d) or in a cytoplasmic with membranous accentuation pattern (c and e). All mucinous carcinoma cases showed the luminal and cytoplasmic pattern (f). Original magnification × 400 (a) and × 400 (b–f)

Fig. 3

Immunohistochemical expression of MUC2 (a), MUC4 (b), MUC5AC (c) and MUC6 (d). Focal weak staining of MUC2 was observed in the cytoplasm of mucinous carcinoma cells (a). Positive expression of MUC4 was observed in invasive ductal carcinoma cells including intracytoplasmic mucin (b). Conspicuous expression of MUC5AC and MUC6 was noted in invasive ductal carcinoma (c) and mucinous carcinoma (d), but not in intracytoplasmic mucin. Original magnification × 400 (a–d)