Elsevier

Human Pathology

Volume 82, December 2018, Pages 158-162
Human Pathology

Original contribution
Can tumor-associated macrophages in ductal carcinoma in situ on biopsy predict invasive carcinoma on excision?

https://doi.org/10.1016/j.humpath.2018.07.023Get rights and content

Highlights

  • M2 macrophages (CD163-positive) may play a role in behavior and progression of DCIS.

  • DCIS-associated CD163 cells were not significantly associated with the presence of invasion.

  • There was no significant correlation between DCIS grade and CD163-positive cells.

Summary

Recent trials have explored surveillance of ductal carcinoma in situ (DCIS) without complete excision, but it is difficult to fully exclude an associated, unsampled invasive focus. Tumor microenvironment, including tumor-associated macrophages, may play a role in the transition from in situ to invasive carcinoma, and the presence of CD163-positive cells with DCIS has been associated with increased risk of progression to invasive carcinoma. We aimed to evaluate the role of DCIS-associated CD163-positive cells on biopsy in predicting associated invasion on excision. Immunohistochemistry for CD163 was performed on 57 total biopsy cases of DCIS of low (n = 13), intermediate (n = 21), and high (n = 23) nuclear grade, 27 (47%) of which showed invasion on the subsequent excision specimen. Positive intratumoral and stromal cells were quantified independently by 2 observers based on the percentage of cells staining. Intratumoral CD163 scores ranged from 0 to 2 (mean, 0.7). Stromal CD163 scores ranged from 0 to 3 (mean, 1.3). Intratumoral and stromal CD163 levels were not significantly associated with the presence of subsequent invasion when evaluated as a whole group (P = .36 and P = .47) or when subdivided into low (P = .36 and P = .17), intermediate (P = .82 and P = .82), or high (P = .09 and P = .68) nuclear grades. There was no correlation between intratumoral CD163 content and DCIS grade (P = .257). A trend for higher stromal CD163 expression was seen with higher-grade DCIS, although not statistically significant (P = .178). In conclusion, CD163 on breast core biopsy does not help select patients who may safely forgo excision of DCIS.

Introduction

The diagnosis of ductal carcinoma in situ (DCIS) of the breast increased significantly in recent decades with the introduction and routine use of mammographic screening in women. National Comprehensive Cancer Network guidelines recommend treatment of DCIS with complete excision with or without adjuvant radiation. Because of the indolent behavior of most cases of DCIS, recent trials have explored active surveillance of DCIS diagnosed on core biopsy, without complete excision. Unfortunately, core biopsy has been reported to underestimate the presence of a synchronous invasive breast cancer in up to 47% of cases [1]. Clinical and histologic features such as mass lesions, high nuclear grade, and the presence of comedonecrosis are associated with higher risk of invasion, but these features have not been shown to reliably predict the presence or absence of an adjacent, unsampled invasive tumor focus [2], [3]. Additional microscopic features and biomarkers have been explored to better predict DCIS behavior. Tumor microenvironment, including the presence of tumor-associated macrophages, may play an important role in the transition from in situ to invasive carcinoma by releasing cytokines, chemokines, and growth factors that contribute to tumor proliferation, progression, and angiogenesis. In particular, type 2, or M2, macrophages have been shown to have protumoral functions in multiple carcinoma types, including breast carcinoma [4]. CD163 is an M2-specific marker that can be used to identify the presence of these particular macrophages in the tumor environment [5]. The presence of CD163-positive cells with DCIS has been shown to be significantly associated with increased risk of progression to invasive carcinoma [6]. The aim of our study was to evaluate the significance of DCIS-associated CD163-positive cells on a breast core biopsy material in predicting adjacent, synchronous invasion on excision.

Section snippets

Materials and methods

After university institutional review board approval, cases of DCIS diagnosed on core biopsy with follow-up excision results were identified by retrospective report search of the electronic pathology database. All cases of low-grade DCIS with subsequent invasion, representing the lowest incidence category in this study, were identified over a 10-year period. Representative matched numbers of cases of low-grade DCIS without invasion as well as intermediate- and high-nuclear-grade DCIS, with and

Results

Fifty-seven total biopsy cases of DCIS were identified to be of low (n = 13), intermediate (n = 21), and high (n = 23) nuclear grade, 27 (47%) of which showed invasion on the subsequent excision specimen. Intratumoral CD163 scores ranged from 0 to 2 (mean, 0.7; Figure B). Stromal CD163 scores ranged from 0 to 3 (mean, 1.3; Figure D). Intratumoral and stromal CD163 levels were not significantly associated with the presence of subsequent invasion when evaluating all combined cases of DCIS

Discussion

With the introduction of routine mammographic screening, the diagnosis of DCIS has increased nearly 5-fold. Current standard of care for DCIS is surgical resection with or without radiation. Because most cases of DCIS are indolent and do not progress to invasive carcinoma [8], surgical management has been questioned recently and less aggressive management options are being pursued. Clinical trials exploring the role of active surveillance of women diagnosed as having DCIS on screening

Conclusions

Although the presence of CD163-positive macrophages has previously been shown to portend increased risk of subsequent DCIS recurrence with invasion, we did not find the presence of such inflammatory cells at the time of diagnostic core biopsy to be predictive of the presence of a concurrent, unsampled invasive tumor. This marker does not therefore seem to be a helpful addition to risk stratification when selecting those patients who may forgo surgical excision.

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  • Disclosures: The authors declare no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sections

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