Expression of PD-L1 and IDO in hormone receptor negative DCIS.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14116-e14116
Author(s):  
Sneha Deepak Phadke ◽  
Gerald H. Clamon ◽  
Amani Bashir ◽  
Matthew Keeney ◽  
Timothy Ginader

e14116 Background: Although outcomes from ductal carcinoma in situ (DCIS) are generally excellent, hormone receptor (HR) negative DCIS is associated with a higher rate of recurrence. There is no chemopreventative agent that has been effective in this subgroup. The aim of our study was to evaluate expression of PD-L1 and IDO (Indoleamine 2,3-Dioxygenase) in HR negative DCIS, in an effort to identify a possible target for prevention using immunotherapy. Methods: Using pathology databases at the University of Iowa, we identified 60 cases of HR negative DCIS from 1995-2017, and 41 of these cases had adequate DCIS tissue for immunostaining. Immunohistochemical staining with antibodies against PD-L1 and IDO was performed on slides prepared from formalin-fixed paraffin-embedded tissue blocks retrieved from pathology archives. IDO was assessed by IHC using the mouse monoclonal antibody clone 10.1 (Millipore Sigma). An initial assessment for PD-L1 (M3653 mouse monoclonal antibody clone 22C3, DAKO) was negative. A repeat assessment for PD-L1 on a smaller sample in a different laboratory was also negative. Clinical data was abstracted from the medical record of each patient. Results: Of the 41 subjects with enough tissue for staining, the median age at diagnosis was 56.76 years, and median BMI was 26.59 kg/m2. Most common method of DCIS detection was screening mammogram (80.5%) versus a patient detected breast finding (19.5%). Most subjects had high grade DCIS (92.7%) and none had low grade DCIS. Six subjects (16.7%) had an ipsilateral in situ recurrence while another 6 subjects developed ipsilateral invasive cancer. Most of the subjects had HER2+ DCIS (63.9%). None of the 41 cases stained positive for IDO or PD-L1, thus no statistical analysis was done to analyze associations with clinicopathologic characteristics. Conclusions: Our sample of HR negative DCIS tumors did not express PD-L1 or IDO, making these receptors unlikely targets for immunopreventative efforts. It is still possible that tumor mutation burden, expression of PD-L2, PD-L1 or IDO expression on TILs, or expression of CTLA-4 may be future considerations for work in the DCIS microenvironment.

1999 ◽  
Vol 435 (4) ◽  
pp. 413-421 ◽  
Author(s):  
Tetsunari Oyama ◽  
Horacio Maluf ◽  
F. Koerner

2014 ◽  
Vol 66 (3) ◽  
pp. 763-768 ◽  
Author(s):  
I.L.D. Silva ◽  
A.P.M. Dias ◽  
A.C. Bertagnolli ◽  
G.D. Cassali ◽  
E. Ferreira

Biomolecular evidence has shown that ductal carcinoma in situ(DCIS) may develop into invasive carcinoma of the canine mammary gland, and mutations in proto-oncogenes HER2 and EGFR; two members of the family of epidermal growth factor receptors, may be involved in this process. The purpose of this study was the characterization of the immunohistochemical expression of the EGFR and HER2 proteins in the process of neoplastic transformation, supposedly present in ductal carcinomas in situin canine mammary glands. Fifteen cases of DCIS were evaluated, with a higher expression of HER2 and EGFR being observed in low-grade carcinomas when compared with high-grade neoplasms, and with a high positive statistical correlation in the latter. Results suggest that aggressive tumors tend to lose the expression of EGFR and HER2 simultaneously. The loss of the expression of these markers may be related to the process of neoplastic progression in canine mammary tumors.


Breast Care ◽  
2019 ◽  
Vol 15 (4) ◽  
pp. 386-391
Author(s):  
Benedict Krischer ◽  
Serafino Forte ◽  
Gad Singer ◽  
Rahel A. Kubik-Huch ◽  
Cornelia Leo

Purpose: The question of overtreatment of ductal carcinoma in situ (DCIS) was raised because a significant proportion of especially low-grade DCIS lesions never progress to invasive cancer. The rationale for the present study was to analyze the value of stereotactic vacuum-assisted biopsy (VAB) for complete removal of DCIS, focusing on the relationship between the absence of residual microcalcifications after stereotactic VAB and the histopathological diagnosis of the definitive surgical specimen. Patients and Methods: Data of 58 consecutive patients diagnosed with DCIS by stereotactic VAB in a single breast center between 2012 and 2017 were analyzed. Patient records from the hospital information system were retrieved, and mammogram reports and images as well as histopathology reports were evaluated. The extent of microcalcifications before and after biopsy as well as the occurrence of DCIS in biopsy and definitive surgical specimens were analyzed and correlated. Results: There was no correlation between the absence of residual microcalcifications in the post-biopsy mammogram and the absence of residual DCIS in the final surgical specimen (p = 0.085). Upstaging to invasive cancer was recorded in 4 cases (13%) but occurred only in the group that had high-grade DCIS on biopsy. Low-grade DCIS was never upgraded to high-grade DCIS in the definitive specimen. Conclusions: The radiological absence of microcalcifications after stereotactic biopsy does not rule out residual DCIS in the final surgical specimen. Since upstaging to invasive cancer is seen in a substantial proportion of high-grade DCIS, the surgical excision of high-grade DCIS should remain the treatment of choice.


2014 ◽  
Vol 80 (10) ◽  
pp. 944-947
Author(s):  
Victoria O'connor ◽  
Elizabeth Arena ◽  
Joslyn Albright ◽  
Nefertiti Brown ◽  
Ryan O'connor ◽  
...  

Radiologic–pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.


2012 ◽  
Vol 36 (8) ◽  
pp. 1247-1252 ◽  
Author(s):  
Sebastian Aulmann ◽  
Lisa Braun ◽  
Friederike Mietzsch ◽  
Thomas Longerich ◽  
Roland Penzel ◽  
...  

2019 ◽  
Vol 153 (3) ◽  
pp. 360-367 ◽  
Author(s):  
Sarah A Alghamdi ◽  
Kritika Krishnamurthy ◽  
Sofia A Garces Narvaez ◽  
Khaled J Algashaamy ◽  
Jessica Aoun ◽  
...  

Abstract Objectives We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. Methods Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. Results Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists’ agreement was poor (κ = 0.235). Conclusions Pathologists’ reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.


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