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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 2  |  Page : 667-670

Critical appraisal of stromal CD10 staining in fibroepithelial lesions of breast with a special emphasis on expression patterns and correlation with WHO grading


1 Department of Pathology, University College of Medical Sciences and GTB Hospital, New Delhi, India
2 Department of Pathology, Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital, New Delhi, India
3 Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India

Date of Web Publication25-Jul-2016

Correspondence Address:
Vandana Puri
Asssistant Professor, Pathology, University College of Medical Sciences and GTB Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.177215

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 > Abstract 


Background: Fibroepithelial lesions of the breast are classified into fibroadenoma and phyllodes tumor (PT). Although WHO has established a well-defined grading system for PT, dilemma of discriminating borderline from malignant PT still exists. Stromal CD10 is a known poor prognostic factor in invasive breast cancer, its expression in fibroepithelial lesions of the breast is not well-documented. Till date, only one study has correlated the CD10 staining score with tumor grade in PT.
Objective: To evaluate whether the differences in expression patterns of CD10 and staining intensity correlate with the degree of malignancy in fibroepithelial tumors of the breast.
Materials and Methods: This is a retrospective study in which stromal CD10 expression was studied in 75 cases of fibroepithelial lesions of the breast using immunohistochemistry. Statistical analysis was performed using Chi-square test.
Results: There was a statistically significant trend of increasing stromal expression of CD10 with increasing degree of malignancy (P = 0.001).
Conclusions: CD10 staining pattern and its scoring can assist the pathologist to accurately grade the PT of the breast for adequate treatment and can also be used as a target for the development of novel therapies.

Keywords: CD10, fibroepithelial tumors breast, phyllodes tumor


How to cite this article:
Puri V, Jain M, Mahajan G, Pujani M. Critical appraisal of stromal CD10 staining in fibroepithelial lesions of breast with a special emphasis on expression patterns and correlation with WHO grading. J Can Res Ther 2016;12:667-70

How to cite this URL:
Puri V, Jain M, Mahajan G, Pujani M. Critical appraisal of stromal CD10 staining in fibroepithelial lesions of breast with a special emphasis on expression patterns and correlation with WHO grading. J Can Res Ther [serial online] 2016 [cited 2019 Dec 10];12:667-70. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/667/177215




 > Introduction Top


Fibroepithelial tumors of the breast are a heterogeneous group of biphasic lesions comprising of an epithelial component and a quantitatively predominant mesenchymal component. These are classified into two major categories: Fibroadenoma and phyllodes tumor (PT).[1]

PTs are graded into benign, borderline and malignant according to WHO classification.[2] The histological criteria used for this grading lack standard interpretation and hence there is an interobserver variability among pathologists.[3] Therefore, multiple immunohistochemical (IHC) markers are being explored to discriminate between the grades of PT and to decrease the diagnostic bias.[3],[4],[5],[6],[7]

CD10 is a zinc-dependent metalloproteinase, which degrades a variety of bioactive peptides. Stromal CD10 expression in invasive breast carcinoma is a poor prognostic marker and a potential target for the development of novel therapies. Unfortunately, CD10 expression in mammary stromal neoplasms is not well-documented, with only occasional studies in literature.

In this study, the IHC expression of CD10 was evaluated in the stromal cells of PTs and fibroadenomas, with the aim of determining whether the degree of CD10 expression in stromal cells is related to the grade of the tumor. To the best of our knowledge, only one study has correlated the grading of CD10 with the tumor grade of PT. The histopathological expression patterns of CD10 in PTs have also not been documented.


 > Materials and Methods Top


This is a retrospective study, where the paraffin wax blocks of 75 fibroepithelial tumors were retrieved from the archives of the department of pathology. Four micrometer thick sections were cut and stained with hematoxylin and eosin. All the slides were reviewed, and all the diagnoses were confirmed histologically as fibroadenomas and PT. The stroma was cellular and expanded in PT, resulting in a leaf-like pattern. The degree of malignancy was assessed using the following histological parameters: (1) stromal cellularity; (2) nuclear pleomorphism; (3) stromal overgrowth; (4) mitotic rate; and (5) margin of the tumor. Parameters 1 and 2 were graded as mild, moderate, or severe. Stromal overgrowth was graded as present (absence of epithelial element within a low power field [10×]) or absent (presence of epithelial element within a low power field [Nikon Labophot; field area, 1.9 mm 2]); and the mitotic count was expressed as the number of mitotic figures per each 10 high power fields (Nikon Labophot; field area, 0.19 mm 2). A diagnosis of benign PT was made when there was low cellularity, no stromal overgrowth, mild pleomorphism, a rounded margin, and a mitotic count of ≤2/10 high power fields. Malignant PT was diagnosed when the mitotic count was ≥5/10 high power fields together with stromal overgrowth and an infiltrative margin. PT of borderline malignancy was diagnosed when the criteria for malignant PT were not totally fulfilled. Diagnosis of fibroadenomas was confirmed when the lesions showed a biphasic pattern, with a bland epithelial component and with the stromal component showing low cellularity, minimal to absent stromal mitoses and the absence of a large frond-like growth pattern of the stroma. For the assessment of CD10 expression, a representative slide from each case was stained using an antibody against CD10 (clone DBS 56C6) with the avidin-biotin method. Stromal cell staining was assessed, using cytoplasmic staining of the breast myoepithelium as an internal control. The staining intensity was graded as negative (<10% stromal cells are positive), weak (10–30% stromal cells are positive), and strong (>30% stromal cells are positive).[8]

The study was approved by the institutional review committee.

Statistical analysis

The Spearman correlation was applied to find the strength of correlation between malignancy grades with subject age and tumor size. The Kendall tau-c was applied to assess the correlation between the malignancy grades and CD10 grades. The data were analyzed using statistical software SPSS version 16. The P < 0.05 was considered as significant.


 > Results Top


The study included 50 cases of fibroadenoma and 25 cases of PT, obtained from the archives of the department of pathology. The patients age ranged from 15 to 62 years (mean 37.4 ± 12.2). Tumor size ranged from 2.5 cm to 18 cm (mean 7.56 ± 4.24). WHO grading of PT was done, and they were classified as benign, borderline and malignant. A total of 16 cases of benign, 6 cases of borderline and 3 cases of malignant PT were included in the study. The details of the age group involved and tumor size in each category are depicted in [Table 1].
Table 1: Comparison of the characteristics of the study group

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There was a progressive increase in age as well as tumor size from fibroadenoma to PT of benign, borderline, and malignant grades. Spearman correlation was applied to find the correlation between the age, size with malignancy, rho value for age and malignancy status was 0.739 (P = 0.000; P< 0.001) and for size and malignancy was 0.669 (P = 0.000, P < 0.001). The positive correlation revealed that grade of malignancy increased with age and size.

CD10 expression in fibroadenoma was limited to myoepithelium, and none of them showed stromal CD10 expression [Figure 1]. 11 out of 16 cases of benign PT were positive for CD10, 6 out of 6 borderline PT were positive for CD10, 3 out of 3 cases of malignant PT were positive for CD10. On grading of CD10, 5 out of 16 (31.25%) benign PT were CD10 negative, 8 out of 16 (50%) belonged to Grade 1, 3 out of 16 (18.75%) belonged to Grade 2. Three out of 6 (50%) borderline belonged to Grade 2 and 3 out of 6 (50%) belonged to Grade 1. None of borderline PTs was CD10 negative. All 3 (100%) malignant PT belonged to Grade 2 CD10 score [Table 2].
Figure 1: Photomicrograph showing CD10 expression in fibroadenoma that is limited only to myoepithelium

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Table 2: CD10 expression profile in the different types of fibroepithelial tumors

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There was a statistically significant trend of increasing CD10 stromal expression with increasing degree of malignancy (P = 0.001). CD10 staining was diffuse and strong in malignant PT [Figure 2]. The staining intensity was strong but patchy in borderline PT [Figure 3]. Both of them showed the strongest staining in the subepithelial region that correlates well with the areas of higher stromal cellularity and mitotic activity. Weak and patchy CD10 staining was seen in Benign PT [Figure 4].
Figure 2: Photomicrograph showing diffuse and strong stromal CD10 staining in malignant phyllodes tumor

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Figure 3: Photomicrograph showing strong and patchy stromal CD10 staining in borderline phyllodes tumor

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Figure 4: Photomicrograph showing patchy CD10 staining was seen in benign phyllodes tumor

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 > Discussion Top


PT accounts for 2.5% of all fibroepithelial lesions of the breast.[9] 85–95% of PT are benign, and approximately 10–15% are malignant. Although WHO has established a grading system, there is no standard interpretation of histologic endpoint criteria, and therefore, diagnosis by different pathologists may vary.[9] This dilemma still exists. Literature reveals varying studies attempting to differentiate benign PT from malignant PT using a variety of IHC stains.

According to a study by Al-Masri et al.[3] CD10 positivity was seen in 82.4% of malignant PT, 60% of borderline PT and 43.8% of benign PT. In our study also, stromal CD10 positivity was seen in 100% malignant, 100% borderline and 68.7% of benign PT though their intensity and staining patterns varied. Similar results were also shown by Mechtersheimer et al.[10]

On grading PT on the basis of CD10, Grade 2 CD10 expression was seen in all the cases of malignant PT, 50% cases of borderline PT and 18.75% of benign PT. Similar trends were shown in a study by Al-Masri et al.[3]

The unpredictable clinical course of PT is demonstrated by several studies that attempted to predict the clinical outcome based solely on histological classification with little or no success.[5] In our study, we found that CD10 staining is strong and diffuse in cases of malignant PTs as against borderline phyllodes that show strong but patchy staining and benign phyllodes that showed weak and patchy staining. None of the studies have described the histopathological patterns of CD10 expression in PT except Tse et al.[5] who showed that CD10 expression tended to occur in the subepithelial location, in the area of sub epithelial-stromal condensation, which is a focus of high proliferative activity. Furthermore, in our study, 3 cases of benign PTs showed Grade 2 stromal CD10 positivity. These cases should be followed up carefully to look for evidence of metastasis. In a study by Al-Masri et al.,[3] there was a statistically correlation between stromal CD10 positivity and metastasis. This can be postulated on the basis that CD10 being a metalloprotease, increases the likelihood of metastasis by providing tumor the potential of invading blood vessels.[5]

Based on WHO criteria, the benign and frankly malignant PT can be easily diagnosed; however, the defining features of borderline phyllodes remain highly variable. Stromal CD10 expression pattern and intensity gives a good accuracy for predicting malignancy in PT and can be used to predict the metastatic risk in PT and thereby allowing a careful follow-up and adequate treatment. Since the number of subjects in the malignant phyllodes group is small, these results need to be applied to a larger group of patients to be more authenticated.

Thus, we suggest that CD10 staining patterns, it is scoring along with the histopathological features can assist the pathologist to accurately grade the PT for adequate treatment.


 > Conclusion Top


CD10 being a metalloprotease, increases the likelihood of metastasis by providing tumor the potential of invading blood vessels. Stromal CD10 expression pattern and intensity gives a good accuracy for predicting malignancy in PT and can be used to predict the metastatic risk in PT and thereby allowing a careful follow-up and adequate treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
World Health Organization. Histological typing of breast tumors. International Histological Classification of Tumors. 2nd ed. Geneva, Switzerland: WHO; 1981.  Back to cited text no. 1
    
2.
Fattaneh A, Devilee P. WHO Classification of Tumors: Tumors of the Breast and Female Genital Organs. Lyon: IARC; 2003.  Back to cited text no. 2
    
3.
Al-Masri M, Darwazeh G, Sawalhi S, Mughrabi A, Sughayer M, Al-Shatti M. Phyllodes tumor of the breast: Role of CD10 in predicting metastasis. Ann Surg Oncol 2012;19:1181-4.  Back to cited text no. 3
    
4.
Chen CM, Chen CJ, Chang CL, Shyu JS, Hsieh HF, Harn HJ. CD34, CD117, and actin expression in phyllodes tumor of the breast. J Surg Res 2000;94:84-91.  Back to cited text no. 4
    
5.
Tse GM, Tsang AK, Putti TC, Scolyer RA, Lui PC, Law BK, et al. Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours. J Clin Pathol 2005;58:185-9.  Back to cited text no. 5
    
6.
Millar EK, Beretov J, Marr P, Sarris M, Clarke RA, Kearsley JH, et al. Malignant phyllodes tumours of the breast display increased stromal p53 protein expression. Histopathology 1999;34:491-6.  Back to cited text no. 6
    
7.
Ibrahim WS. Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients. Indian J Pathol Microbiol 2011;54:741-4.  Back to cited text no. 7
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8.
Puri V, Jain M, Thomas S. Stromal expression of CD10 in invasive breast carcinoma and its correlation with ER, PR, HER2-neu, and Ki67. Int J Breast Cancer 2011;2011:437957.  Back to cited text no. 8
    
9.
Tsai WC, Jin JS, Yu JC, Sheu LF. CD10, actin, and vimentin expression in breast phyllodes tumors correlates with tumor grades of the WHO grading system. Int J Surg Pathol 2006;14:127-31.  Back to cited text no. 9
    
10.
Mechtersheimer G, Krüger KH, Born IA, Möller P. Antigenic profile of mammary fibroadenoma and cystosarcoma phyllodes. A study using antibodies to estrogen- and progesterone receptors and to a panel of cell surface molecules. Pathol Res Pract 1990;186:427-38.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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