Journal of Pathology and Translational Medicine

Original Articles

Clinicopathologic characteristics of HER2-positive pure mucinous carcinoma of the breast: Yunjeong Jang, Hera Jung, Han-Na Kim, Youjeong Seo, Emad Alsharif, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Yeon Hee Park, Eun Yoon Cho, Soo Youn Cho; J Pathol Transl Med. 2020;54(1):95-102. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.24

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Background
Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated.
Methods
Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases.
Results
There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS.
Conclusions
Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.

Citations

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Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases
Min Han, Daniel Schmolze, Javier A. Arias-Stella, Christina H. Wei, Joanne Mortimer, Fang Fan
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Dinesh Chandra Doval, Rupal Tripathi, Sunil Pasricha, Pankaj Goyal, Chaturbhuj Agrawal, Anurag Mehta
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Methylation and Immunoexpression of p16^INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16^INK4a Hypermethylation in Plasma by Real-Time PCR: Jae Jun Lee, Eunkyung Ko, Junhun Cho, Ha Young Park, Jeong Eon Lee, Seok Jin Nam, Duk-Hwan Kim, Eun Yoon Cho; Korean J Pathol. 2012;46(6):554-561. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.554

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Abstract PDF

Background

The p16^INK4a gene methylation has been reported to be a major tumorigenic mechanism.

Methods

We evaluated the methylation status of the p16^INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16^INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay.

Results

The frequencies of p16^INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16^INK4a was significantly higher in the cancer patients than the normal controls (p<0.001).

Conclusions

High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16^INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.

Citations

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