Extensive Retraction Artifact Correlates With Lymphatic Invasion and Nodal Metastasis and Predicts Poor Outcome in Early Stage Breast Carcinoma

Abstract

Retraction artifact resulting in clear spaces around tumor cell nests is frequently seen in histologic material and may present difficulty in their differentiation from lymphovascular invasion. We noticed that retraction artifact seemed to be more common around groups of breast cancer cells compared with benign acini, and when extensively present, metastasis to axillary lymph nodes was often seen. Thus, we performed a study of 304 cases of stage pT1 and pT2 breast carcinomas to test our hypothesis that extensive retraction artifact in tumors correlates with lymphatic spread and outcome. Tumors were evaluated to determine the presence and extent of retraction artifact around tumor cell nests and the presence of lymphatic invasion. Lymphatic invasion was confirmed by D2-40 immunostaining. The extent of retraction artifact in tumors was correlated with clinicopathologic tumor features and patient outcome. Variable degree of retraction artifact was present in 183 of 304 (60%) invasive carcinomas, with its extent ranging from 0% to 90% (median 5%). The extent of retraction artifact showed a significant correlation with tumor size, histologic type, histologic grade, presence of lymphovascular invasion, and nodal metastasis. Further, extensive retraction artifact was significantly associated with poor overall and disease-free survival in both univariate and multivariate analyses. We propose that the apparent retraction of the stroma from cells of invasive breast carcinoma on routine histologic sections is not a phenomenon merely due to inadequate fixation as currently believed. Rather, it likely signifies important biologic changes that alter tumor-stromal interactions and contribute to lymphatic spread and tumor progression.

Periacinar Retraction Clefting and D2-40 Expression in Prostatic Adenocarcinoma

“…Acs and co-workers found that breast carcinomas associated with lymphovascular invasion and lymph node metastasis had significantly higher percentage of retraction artifacts compared to tumors without these features. Furthermore, extensive retractions were significantly associated with both poor overall prognosis and disease-free interval [12]. Recently, same authors have confirmed these findings in core needle biopsy material of invasive ductal carcinoma [13].…”

“…However, in our opinion they probably result from lack of basal cells and/or stromal changes [10,11]. Some authors suggest that the presence and extent of clefts around tumorous tissue, not only in prostatic adenocarcinoma but also in some other tumors, especially breast carcinoma, can predict nodal metastasis and patients' outcome [12][13][14]. Moreover, the presence of extensive retraction clefting in prostatic carcinoma is associated with more aggressive tumor phenotype and a shorter biochemical recurrence-free interval [15].…”

The extent of retraction clefts correlates with lymphatic vessel density and VEGF-C expression and predicts nodal metastasis and poor prognosis in early-stage breast carcinoma

“…Tumor cells, glands and nests surrounded by a clear space without an endothelial lining, which separated the tumor cells from the adjacent stroma, were considered as retraction clefts (Figure 1a). 16,17 Tumors were evaluated to determine the presence or absence of lymphatic invasion based on all available tumor sections. The presence of lymphatic invasion and/or the lack of a lymphatic endothelial lining associated with retracted stroma was confirmed in each case by highlighting the lymphatic vessels using immunohistochemical stains for podoplanin (Figures 1b-f).…”

“…The presence of lymphatic invasion and/or the lack of a lymphatic endothelial lining associated with retracted stroma was confirmed in each case by highlighting the lymphatic vessels using immunohistochemical stains for podoplanin (Figures 1b-f). 19 Based on the results of prior studies, 16,17 cases having retraction clefts involving at least 20% of the tumors were considered to show 'extensive retraction clefts'; this cutoff value also corresponded to the mean value for all tumors.…”

“…14,15 We have recently reported that retraction clefts around tumor cell nests are commonly seen in invasive ductal (no special type) carcinomas of the breast. 16,17 We have shown that the extent of retraction clefts correlates significantly with tumor size and histological grade, and shows a strong association with lymphatic invasion and nodal metastases. We have proposed that retraction clefts seen around tumor cell nests and glands in invasive ductal carcinomas are likely a morphological reflection of altered tumor-stromal interactions, which may contribute to tumor progression and lymphatic spread observed in these patients.…”