Intense basolateral membrane staining indicates HER2 positivity in invasive micropapillary breast carcinoma

• Published in: Modern pathology Vol. 33; no. 7; pp. 1275 - 1286
• Main Authors: Zhou, Shuling, Yang, Fei, Bai, Qianming, Li, Anqi, Li, Ming, Zhong, Siyuan, Lv, Hong, Shui, Ruohong, Tu, Xiaoyu, Bi, Rui, Xu, Xiaoli, Cheng, Yufan, Yu, Baohua, Tang, Shaoxian, Sun, Xiangjie, Zhou, Xiaoyan, Yang, Wentao
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2020; Elsevier Limited
• Subjects: 38; 38/32; 631/67/1347; 692/699/67/1347; 82; 82/51; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - metabolism; ErbB-2 protein; Estrogen receptors; Female; Gene amplification; Humans; Hybridization; Immunohistochemistry - standards; Invasiveness; Laboratory Medicine; Medicine; Medicine & Public Health; Metastases; Middle Aged; Oncology; Pathology; Polarity; Progesterone; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - biosynthesis; Tumors
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-020-0461-z

Invasive micropapillary carcinoma is characterized by the inside-out growth of tumor clusters and displays incomplete membrane immunostaining of
HER2
. According to the 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP)
HER2
-testing recommendation, moderate to intense but incomplete staining could be scored as immunohistochemical 2+. Furthermore, the criteria of immunohistochemical 3+ for this staining pattern are not mentioned. One hundred and forty-seven cases of invasive micropapillary carcinoma with moderate-to-intense
HER2
immunostaining were enrolled. Invasive micropapillary carcinoma components of all cases were scored as immunohistochemical 2+ based on the 2018 ASCO/CAP recommendation. The invasive micropapillary carcinoma component varied from 10% to 100% (mean, 80%). Invasive micropapillary carcinoma components of all 147 tumors exhibited reversed polarity and incomplete basolateral
HER2
membrane staining. One hundred and seventeen of the tumors (80%, 117/147) had moderate staining, and 38 (32%, 38/117) showed
HER2
gene amplification by fluorescence in-situ hybridization.
HER2
gene was amplified in all the remaining 30 tumors (20%, 30/147) that exhibited intense basolateral membrane staining. Besides, average
HER2
signals per cell and ratio of
HER2
/CEP17 were significantly higher in the intense-staining tumors compared with the moderate-staining tumors (
p
 < 0.0001). Follow-up data were available for 140 patients. None of the patients were died. The follow-up time ranged from 1 month to 99 months (median, 57 months). Thirteen (9%, 13/140) patients exhibited disease progression (recurrence or metastasis).
HER2
gene amplification was correlated inversely with estrogen receptor (
p
 = 0.000) and progesterone receptor (
p
 = 0.000) expression, and positively with histological grade (
p
 = 0.003) and disease progression (
p
 = 0.000). Invasive micropapillary carcinoma with intense clear linear basolateral membrane immunostaining indicates
HER2
positivity, even if the staining is incomplete. They should be classified as immunohistochemical 3+ rather than immunohistochemical 2+, which would avoid further fluorescence in-situ hybridization-testing procedure and greatly save the related time, labor, and financial costs. Ultimately, ensure all patients with
HER2
gene amplification obtain effective targeted therapy in time.