Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma

Abstract

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

The Prognostic Potential of Neurokinin 1 Receptor in Breast Cancer and Its Relationship with Ki-67 Index

“…NK1R could be a useful marker that provides clues about prognosis and response to therapy and may represent a new therapeutic target in breast cancer. Few studies are available that explore NK1R expression and investigate its prognostic value in breast cancer [ 12 , 20 – 22 ]. This study retrospectively evaluated the expression of NK1R in 164 breast invasive ductal carcinoma cases from the four molecular subtypes.…”

“…In concordance with our results, one previous study revealed a significant association between NK1R expression and tumor grade, but differential expression among the three grades was not reported in that study [ 23 ]. In another study, high NK1R expression was evident in grade II and grade III breast cancer tissues but analysis for statistically significant difference between grades was not performed [ 12 ]. These findings indicate a prognostic value of NK1R in breast cancer patients.…”

“…NK1R is under investigation as a potential biomarker and therapeutic target in cancer including breast cancer [ 7 – 11 ]. The NK1R was overexpressed in different types of cancers [ 7 , 12 ] and was associated with several carcinogenesis processes such as angiogenesis, proliferation, apoptosis, and metastasis [ 7 , 13 , 14 ]. Additionally, knockdown of NK1R gene or treatment of cancer cells with NK1R antagonists such as aprepitant exerted multiple antitumoral effects [ 7 , 9 , 15 – 17 ].…”

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma

“…It also regulates a variety of biological processes after binding to NK-1R [16] such as cardiac conduction system [26], respiratory physiology [47], immune system regulation [33], sensory perceptions [24], pain processing [25] and inflammation [42]. Enhanced expression of SP/NK-1R has been reported in several pathological entities such as breast cancers [30], ovarian cancers [45], oral squamous cell [15,32], pancreatic cancers [12] and thyroid cancers [20].…”

“…The common etiological factors include smoking, consumption of alcohol, human papillomavirus (HPV), substance abuse such as pan chewing [44,49]. Previously, we investigated the immunolocalization of SP in OSCCs [32], breast carcinomas [30], products of conception (POCs) [4], dental pulp inflammation [31] and COVID-19 patients [29,33].…”