Evidence map›Paper›PMID 36503417›Full record

ArticleBMC cancer2022

Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases.

S Voutilainen, P Heikkilä, J Bartkova, H Nevanlinna, C Blomqvist, J Bartek, J Mattson

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

S VoutilainenHelsinki University Hospital Comprehensive Cancer Centre, Paciuksenkatu 3, PO BOX 180, 00290, Helsinki, Finland. sari.j.voutilainen@hus.fi.ORCID http://orcid.org/0000-0001-7305-9706
P HeikkiläDepartment of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
J BartkovaDanish Cancer Society Research Center, Copenhagen, Denmark.
H NevanlinnaDepartment of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
C BlomqvistHelsinki University Hospital Comprehensive Cancer Centre, Paciuksenkatu 3, PO BOX 180, 00290, Helsinki, Finland.
J BartekDanish Cancer Society Research Center, Copenhagen, Denmark.
J MattsonHelsinki University Hospital Comprehensive Cancer Centre, Paciuksenkatu 3, PO BOX 180, 00290, Helsinki, Finland.
Helsinki University Hospital · FIScience for Life Laboratory · SEUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) - positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC.

methodsA total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome.

resultsAll tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest.

conclusionsMpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.

Indexed as

Carcinoma, Squamous CellTriple Negative Breast NeoplasmsB7-H1 AntigenBiomarkers, TumorHumansLymphocytes, Tumor-InfiltratingPrognosisTumor Suppressor Protein p53B7-H1 AntigenBiomarkers, TumorCD274 protein, humanTumor Suppressor Protein p53Metaplastic breast cancerp53PD-L1RPA2TILsγH2AX

Identifiers

PMID36503417
PMCPMC9743555
OpenAlexW4311125277

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.