| Abstract|| |
Background: In core needle biopsy (CNB) often the histological grade of invasive breast carcinoma is under-estimated due to heterogeneity of epithelial component. Stroma is relatively homogenous throughout the tumor and strong CD10 stromal positivity is proposed to be associated with high tumor grade. Aims and Objectives: The aim of this work was to study the expression of CD10 in stromal cells of invasive carcinoma of breast, no specific type (NST) in CNB specimens, and analyze its association with final histological grade and lymphovascular invasion (LVI). Materials and Methods:A total of 50 cases of invasive carcinoma of breast, NST were studied for 18 months. CNB specimens were graded according to modified Scarff–Bloom–Richardson (SBR) system and CD10 positivity was assessed in stromal cells. Mastectomy specimens were also similarly graded. Relation of stromal CD10 positivity with histological grading and LVI was studied. Statistics: Associations between the variables were studied by Chi-square test. A value of P < 0.05 was considered to be statistically significant. Results:On CNB 46% patients had a grade 2 tumor, followed by 30% grade 3 and 24% grade 1 tumor. Strong CD10 positivity was seen in 40% cases, 32% showed weak positivity and 28% were negative for CD10 in stromal cells in CNB specimen. On evaluation of mastectomy specimen 48% of the patients had a grade 2 tumor, followed by 40% grade 3 tumor and 12% grade 1 tumor. Strong CD10 positivity was found to be significantly associated with final grade 3 tumor (P < 0.001) and LVI (P = 0.005). Conclusions: There was underestimation of histological grade on CNB, while strong stromal CD10 positivity in CNB was significantly associated with final grade 3 tumor and LVI.
Keywords: CD10 positivity, histopathological grading, invasive breast carcinoma
|How to cite this article:|
Boler AK, Akhtar S, Bandyopadhyay A, Bandyopadhyay G. A study of CD10 positivity of stromal cells in core needle biopsy specimen of breast cancer patients and its relation with histological grade and lymphovascular invasion. Indian J Pathol Microbiol 2021;64:460-3
|How to cite this URL:|
Boler AK, Akhtar S, Bandyopadhyay A, Bandyopadhyay G. A study of CD10 positivity of stromal cells in core needle biopsy specimen of breast cancer patients and its relation with histological grade and lymphovascular invasion. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 28];64:460-3. Available from: https://www.ijpmonline.org/text.asp?2021/64/3/460/322404
| Introduction|| |
CNB is the method of choice for pre-operative assessment of breast lumps. But, due to heterogeneity of epithelial component often the histological grade of invasive breast carcinoma is underestimated by CNB., There may be false-negative results also. Tumor stroma can contain more prognostic information than the epithelial component of the tumor. Stromal cells in breast carcinoma may express CD10 which is a zinc-dependent metalloproteinase. It can cleave the matrix and help in tumor invasion and metastasis. CD10 can also cleave doxorubicin leading to resistance to doxorubicin. Strong CD10 stromal positivity is found to be associated with high tumor grade. Assessment of stromal CD10 positivity in small biopsies may thus help in assessment of prognosis and deciding the treatment.
Aims and objectives
- To study the expression of CD10 in stromal cells of invasive carcinoma of breast, NST in CNB specimens
- Analyze the association of stromal CD10 positivity with final histological grade and lymphovascular invasion.
| Materials and Methods|| |
After getting approval from the institutional ethics committee, this prospective study was conducted. Clinical findings were recorded in every patient, who underwent CNB for breast lump from March 2017 to August 2018. Total 50 cases of invasive carcinoma of breast NST diagnosed by CNB and later received as mastectomy specimen were selected for the study excluding male breast carcinoma. Histological findings of the CNB specimen were noted including modified SBR score [Table 1].
Immunohistochemistry (IHC) was done on CNB specimens for stromal CD10 positivity and it was categorized as per criteria shown in [Table 2]. CD10 clone-56C6, Mouse Monoclonal, Batch#0000033932 produced by Cellmarque, USA was used for IHC. Similarly, after obtaining the surgical (mastectomy) specimen H and E stained sections were prepared and histopathological (HP) findings were noted including final modified SBR score.
Statistical analysis was done with the help of MS Excel sheet and SPSS version 25 software. Associations between the variables were assessed by Chi-square test and Fisher's exact test. A value of P < 0.05 was considered statistically significant.
| Results|| |
Peak age of incidence of breast cancer in this study was 41–45 years (30%). Majority (44%) had parity 03, gave a history of breastfeeding (96%), and were aged 20 years or more at the time of first childbirth (74%). Maximum number of the patients presented with a pT3 (60%), followed by pT2 (34%) and pT4 (6%) tumor at the time of mastectomy. There were 52% of the patients categorized as pN1, 36% were pN0 and 12% were pN2. PET (positron emission tomography) report was not available for any patients neither they had any symptoms indicating metastasis, so could not comment on presence or absence of distant metastasis.
Maximum (46%) patients were diagnosed to have a grade 2, 30% grade 3 and 24% grade 1 tumor on CNB. 40% showed strong CD10 positivity, 32% showed weak positivity and 28% were negative for CD10 in stromal cells. In mastectomy specimens 48% had grade 2, 40% had grade 3 and 12% had a grade 1 tumor. LVI was seen in 26% of the cases.
There was underestimation of grade by CNB in 22% of the patients [Figure 1]. After mastectomy 12% cases were upgraded from grade 1 to grade 2 and 10% were upgraded from grade 2 to grade 3.Total score was underestimated in 48% of the CNB. Mitotic count was the most commonly underestimated (30%), followed by tubule formation (16%) and nuclear pleomorphism (14%).
|Figure 1: (a) Photomicrograph from CNB specimen showing grade 2 tumor with tubule formation >10%, H and E, 40x. (b) IHC for CD10 showing strong positivity in stromal cells, 40x. (c) Mastectomy sample received after 3 months of initial diagnosis, specimen was staged as pT4N2Mx. (d) HP section from mastectomy specimen showing a grade 3 tumor with lack of tubule formation. H and E, 40x|
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75% of the grade 3 tumors were correctly diagnosed as grade 3 by CNB. Approximately 70.83% of grade 2 tumors were correctly diagnosed by CNB as grade 2 [Figure 2]. We did not have any case that was overestimated by CNB. Among the high grade (grade 3) tumors 80% showed strong CD10 positivity and 20% high-grade tumors showed weak CD10 positivity.
|Figure 2: (a and b) Stroma predominant CNB specimen showing features of a grade 2 tumor. H and E, 5x and 10x. (c) IHC for CD10 showing weak positivity, <30% stromal cells are positive. 5x. (d) HP section from Mastectomy specimen showing a grade 2 tumor staged as pT2N1Mx|
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Strong CD10 positivity was found to be significantly associated with high-tumor grade (P < 0.001) and odd ratio 26.00. Strong CD10 positivity was also found to be significantly associated with LVI (P 0.005).
| Discussion|| |
The peak age of incidence in our study population was 41–45 years, which is much lower when compared to the Western countries where peak age is 60-70 years. Leong et al., Nandakumar et al. and Toi et al. have also found that in Asian countries including India maximum incidence of breast cancer occur at a younger age than Western Countries.,, In our study, most patients presented at a later stage than those in Western Countries. Saxena et al. found similar results in his studies conducted in India. We can conclude that Indian women are presenting with breast carcinoma at a younger age and later stage than women in western countries. Unfortunately, due to unavailability of PET scan reports of the patients we could not exclude distance metastasis in our patients which was a limitation in our studies.
There was underestimation of grade by CNB in 22% of the patients. Stromal cells of invasive breast carcinoma may express CD10 which is absent in stromal cells of normal breast tissue. Myoepithelial cells express CD10 and serve as a positive control. Most of the previous studies have discussed CD10 positivity in tumor stromal cells obtained from surgical specimen. In our study, we applied IHC for CD10 on CNB specimen. As CNB is done pre-operatively, it can help better in planning of further treatment. In our study, Strong CD10 positivity was found to be significantly associated with grade 3 tumor. Similar results were obtained by Jana et al., Makretsov et al. and Ali et al.,, We also found that strong CD10 positivity is significantly associated with lymphovascular invasion. Similar findings were obtained by study conducted by Ali et al. LVI is an important and independent prognostic marker associated with worse clinical outcome in breast cancer.,,
So, assessment of stromal CD10 positivity in CNB specimen can supplement the grading.
Other recent studies have found stromal CD10 positivity to be significantly associated with lymph node metastasis, ER negativity, Her2/neu positivity and Ki67 positivity.,
Assessment of CD10 positivity can also be useful in cases where epithelial component shows extensive necrosis [Figure 3] or in a core with relative paucity of epithelial component but well-preserved stroma.
|Figure 3: (a) Epithelial component of CNB specimen was extensively necrosed but stroma was well preserved. (b and c) IHC for CD10 shows strong positivity in stromal cells. 5x and 40x. (d) HP section from mastectomy specimen showing extensively necrosed grade 3 tumour, H and E, 10x|
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As CD10 cleaves doxorubicin, its expression may indicate resistance to doxorubicin-based chemotherapeutic regimens. Routine assessment of CD10 positivity can thus help in deciding the treatment regimen. It can also be a therapeutic target for increasing sensitivity for doxorubicin and for inhibiting metastasis as cleaving of matrix by CD10 can promote metastasis.
Informed written consents were obtained from the patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Dr. Santanu Sarkar, Department of General Surgery, Burdwan Medical College, West Bengal.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]