Immunohistochemical Expression of ROS1 in invasive ductal carcinoma of breast in association with hormonal receptor status and Her2Neu expression

Authors

  • Muhammad Umair
  • Ahmed Ahson Khan
  • Nighat Jamal
  • Akhter Ali Bajwa
  • Tabish Hassan
  • Muhammad Umair Khan

DOI:

https://doi.org/10.51985/JBUMDC2024354

Keywords:

Invasive breast carcinoma, ROS1, Estrogen receptor, Progesterone receptor, HER2

Abstract

Objective: To determine the frequency of immunohistochemical expression of ROS1 in invasive ductal carcinoma of the breast in relation to hormonal receptor status and HER2 expression.

 

Study Design and Setting: Descriptive cross-sectional study. Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from May 2022 to Dec 2022.

 

Methodology: This study was conducted on a sample size comprising 137 patients diagnosed with invasive breast carcinoma (ductal carcinoma) on histopathological biopsy specimen. Immunohistochemistry was performed using ROS1, estrogen receptor, progesterone receptor and HER2 antibodies on patients’ tissue samples. Results were interpreted by two independent histopathologists. Finally data was analyzed using SPSS version 25.

 

Results: The mean age of sample population was 50.85 ± 12.17 years. 131 patients were women and 6 were men. ROS1 was positive in 54 cases. ROS1 shows weak staining in 41 cases and moderate to strong staining in 13 cases. ER and PR showed no significant statistical correlation with ROS1 expression. HER2 was positive in 37 cases, equivocal in 11 cases and negative in 89 cases. A significant statistical correlation was seen between ROS1 and HER2 as 23 of HER2 positive cases showed ROS1 expression (p=<0.001).

 

Conclusion: Significant number of ROS1 expressing cases in invasive breast carcinoma can be more revealing in the understanding of pathogenesis of breast carcinoma. In addition, it can also lead to use of certain recent tyrosine kinase inhibitors for treatment of this most common carcinoma in females.

References

Breast cancer. Who.int. [cited 2024 Jul 2]. Available from:

https://www.who.int/news-room/fact-sheets/detail/breastcancer

Khan NH, Duan S-F, Wu D-D, Ji X-Y. Better reporting and

awareness campaigns needed for breast cancer in Pakistani

women. Cancer Manag Res. 2021;13:2125–9. http://dx.doi.org

/10.2147/cmar.s270671

Invasive ductal carcinoma (IDC): Grade, symptoms & diagnosis. Breastcancer.org. [cited 2024 Jul 2]. https://www

.breastcancer.org/types/invasive-ductal-carcinoma

Lin JJ, Shaw AT. Recent Advances in Targeting ROS1 in

Lung Cancer. J Thorac Oncol. 2017;12(11):1611- 1625. doi:

1016/j.jtho.2017.08.002

Davies KD, Doebele RC. Molecular pathways: ROS1 fusion

proteins in cancer. Clin Cancer Res. 2013;19(15):4040–5.

http://dx.doi.org/10.1158/1078-0432.ccr-12-2851

Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi

GR, Arensmeyer KE, et al. New targets in lung cancer. Curr

Oncol Rep. 2020;22(5). Available from: http://dx.doi.org/

1007/s11912-020-00909-8

Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano

S, et al. RET, ROS1 and ALK fusions in lung cancer. Nat

Med. 2012;18(3):378–81. Available from: http://dx.doi.org/

1038/nm.2658

Rimkunas VM, Crosby KE, Li D, Hu Y, Kelly ME, Gu T-L,

et al. Analysis of receptor tyrosine kinase ROS1-positive

tumors in non–small cell lung cancer: Identification of a FIGROS1 fusion. Clin Cancer Res. 2012;18(16):4449–57. Available from: http://dx.doi.org/10.1158/1078-0432.ccr-11-3351

Fielder T, Butler J, Tierney G, Holmes M, Lam KY, Satgunaseelan L, et al. ROS1 rearrangements in lung adenocarcinomas are defined by diffuse strong immunohistochemical

expression of ROS1. Pathology 2022;54(4):399–403. Available

from: dx.doi.org/ 10.1016/ j.pathol.2021.07.012

Huang RSP, Smith D, Le CH, Liu W-W, Ordinario E, Manohar

C, et al. Correlation of ROS1 immunohistochemistry with

ROS1 fusion status determined by fluorescence in situ hybridization. Arch Pathol Lab Med. 2020;144(6):735–41. Available

from: dx.doi.org/10.5858/arpa.2019-0085-oa

Schlam I, Swain SM. HER2-positive breast cancer and tyrosine

kinase inhibitors: the time is now. NPJ Breast Cancer.

;7(1). Available from: http://dx.doi.org/10.1038/s41523-

-00265-1

Andrechek ER, Muller WJ. Tyrosine kinase signalling in

breast cancer: Tyrosine kinase-mediated signal transduction

in transgenic mouse models of human breast cancer. Breast

Cancer Res. 2000;2(3). Available from: http://dx.doi.org

/10.1186/bcr56

Researchgate.net. [cited 2024 Jul 2]. Available from: https://www.researchgate.net/profile / Ameer-Hameedi / publication / 348729528_Immunohistochemical_ Expression_

Of_ROS- 1 _In_ Mammary_ Ductal Carcinoma_ In_ Correlation_ With _Hormonal_ Receptor_ Status_ And_ Her2Neu_

Expression / links / 600d2d6045851553a067a698 / Immunohistochemical – Expression – Of - ROS-1 – In - Mammary

– Ductal - Carcinoma – In – Correlation - With – Hormonal

– Receptor – Status – And - Her2Neu - Expression.pdf

Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Cap.org.

[cited 2024 Jul 2].

Facchinetti F, Friboulet L. Profile of entrectinib and its

potential in the treatment of ROS1-positive NSCLC: evidence

to date. Lung Cancer (Auckl). 2019;10:87–94. Available from:

http://dx.doi.org/10.2147/lctt.s190786

Shaw AT, Hsu PP, Awad MM, Engelman JA. Tyrosine kinase

gene rearrangements in epithelial malignancies. Nat Rev

Cancer. 2013;13(11):772–87. Available from: http://dx.doi.org

/10.1038/nrc3612

Pal P, Khan Z. ROS1-1. J Clin Pathol. 2017;70(12):1001–9.

Available from: http://dx.doi.org/10.1136/jclinpath-2016-

Yoshida A, Tsuta K, Wakai S, Arai Y, Asamura H, Shibata T,

et al. Immunohistochemical detection of ROS1 is useful for

identifying ROS1 rearrangements in lung cancers. Mod Pathol.

;27(5):711–20. Available from: http://dx.doi.org/10.1038/

modpathol.2013.192

Viale G. The current state of breast cancer classification. Ann

Oncol. 2012;23:x207–10. Available from: http://dx.doi.org/10

.1093/annonc/mds326

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann

B, Senn H-J. Strategies for subtypes—dealing with the diversity

of breast cancer: highlights of the St Gallen International

Expert Consensus on the Primary Therapy of Early Breast

Cancer 2011. Ann Oncol. 2011;22(8):1736–47. Available

from: http://dx.doi.org/10.1093/annonc/mdr304

Eom M, Lkhagvadorj S, Oh SS, Han A, Park KH. ROS1

expression in invasive ductal carcinoma of the breast related

to proliferation activity. Yonsei Med J. 2013;54(3):650.

Available from: http://dx.doi.org/10.3349/ymj.2013.54.3.650

Raut A, Yeap I, Mylchreest L, Mills J, Watson N, Gill AJ.

ROS1 immunohistochemistry is not a worthwhile screening

test in breast carcinoma. Pathology. 2015;47:S106. Available

from: http://dx.doi.org/10.1097/01. pat.0000461629.05041.4e

Li K, Liao N, Chen B, Zhang G, Wang Y, Guo L, et al. Genetic

mutation profile of Chinese HER2-positive breast cancers

and genetic predictors of responses to Neoadjuvant anti-HER2

therapy. Breast Cancer Res Treat. 2020;183(2):321–32. Available from: http://dx.doi.org/10.1007/s10549-020-05778-0

Eggemann H, Ignatov T, Burger E, Kantelhardt EJ, Fettke F,

Thomssen C, et al. Moderate HER2 expression as a prognostic

factor in hormone receptor positive breast cancer. Endocr

Relat Cancer. 2015;22(5):725–33. Available from: http://dx.doi.org/10.1530/erc-15-0335

Force J, Sokol ES, Taylor ML, Huang D, Marcom PK, Davare

M, et al. Abstract P3-06-09: Incidence of ROS1 genomic

alterations in breast cancer. Cancer Res. 2020;80 (4_ Supplement): P3-06-09-P3-06–9. Available from: http://dx.doi.

org/10.1158/1538-7445.sabcs19-p3-06-09

O’Neil SR, Weber GA, Deming DA, Burkard ME, Kenny

PA, Richmond CS, et al. Exceptional response to crizotinib

with subsequent response to cabozantinib in metastatic, ROS1-

GOPC fusion–mutated breast cancer. JCO Precis Oncol.

;(7). Available from: http://dx.doi.org /10.1200/po.23.001

Downloads

Published

2024-10-08

How to Cite

Umair, M. ., Khan, A. A. ., Jamal, N. ., Bajwa, A. A. ., Hassan, T. ., & Khan, M. U. . (2024). Immunohistochemical Expression of ROS1 in invasive ductal carcinoma of breast in association with hormonal receptor status and Her2Neu expression. Journal of Bahria University Medical and Dental College, 14(04), 227–232. https://doi.org/10.51985/JBUMDC2024354

Issue

Section

Original Articles