Journal of Cytology
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 26  |  Issue : 2  |  Page : 65-68
Role of cytologic grading in prognostication of invasive breast carcinoma


1 Department of Pathology, J.N. Medical College, A.M.U., Aligarh - 202 002, India
2 Department of Surgery, J.N. Medical College, A.M.U., Aligarh - 202 002, India

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Date of Web Publication26-Aug-2009
 

   Abstract 

Background: Evaluation of cytologic features is indispensable in the preoperative diagnosis and grading of infiltrating ductal breast carcinoma (CA) in fine-needle aspiration cytology (FNAC) material and this method can also provide additional information regarding intrinsic features of the tumor as well as its prognosis.
Aim: This study has been done to evaluate comparatively the cytologic and histomorphologic grading of infiltrating ductal carcinoma of breast with specific reference to lymph node metastasis and its role in prognostication.
Materials and Methods: Forty three patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were cytologically and histologically graded (employing Robinson's cytologic grading system and Elston's modification of Bloom-Richardson system, respectively). Statistical analysis was done employing 'z' test and c2 test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases, graded cyto-histologically were also evaluated for presence or absence of metastasis to the regional lymph nodes employing c2 test.
Results: With histologic grade taken as the standard, cytology was found to be fairly comparable, for grading breast carcinoma (overall sensitivity 89.1%, specificity 100%). Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histologic grading was insignificant in all the three grade (p > 0.05). Of the six parameters studied, cell dissociation, nucleoli and chromatin pattern were the most influential features (p < 0.001). The statistically significant difference (p < 0.001) was found in incidences of axillary lymph node metastatic rate in three cytologic grades (15.4% in grade I vs. 83.3% in grade III) as well.
Conclusions: Apart from being simple and noninvasive, cytologic grading is comparable to histologic grading and might provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting mode of therapy and to predict tumor behavior.

Keywords: Axillary metastasis; comparative cyto-prognostic grading; infiltrating ductal carcinoma.

How to cite this article:
Khan N, Afroz N, Rana F, Khan M A. Role of cytologic grading in prognostication of invasive breast carcinoma. J Cytol 2009;26:65-8

How to cite this URL:
Khan N, Afroz N, Rana F, Khan M A. Role of cytologic grading in prognostication of invasive breast carcinoma. J Cytol [serial online] 2009 [cited 2019 Sep 19];26:65-8. Available from: http://www.jcytol.org/text.asp?2009/26/2/65/55224



   Introduction Top


Breast cancer is a malignant disease with a heterogenous prognosis; evaluation of possible prognostic parameters is of growing interest. These include lymph node status, [1] estrogen receptor status, [2] tumor histologic grading [3] and cell proliferation index. [4] Although all these parameters have been well studied on surgical specimens, the evaluation of cytologic features of infiltrating ductal breast carcinoma (CA) in fine-needle aspiration cytology (FNAC) material is valuable and a number of authors, [5],[6] have shown that this method can provide additional information regarding intrinsic features of the tumor as well as its prognosis. The information provided by FNAC can be extremely useful when establishing the best neoadjuvant therapy for patients for whom surgical removal of the tumor is not the best option. [7] Cytologic grading based on Papanicolaou staining can be done easily in every hospital and such grading would allow assessment of the tumor in situ, so that not only the most suitable treatment could be selected before primary surgery, but also the morbidity associated with over treatment of low grade tumors could be avoided. [8]


   Materials and Methods Top


Forty three cases undergoing surgery at J.N. Medical College, Aligarh, were selected who were diagnosed as invasive ductal carcinoma of the breast. In all cases the preoperative diagnosis following FNA was carcinoma. The FNAC material was fixed with 95% alcohol and stained using the routine Papanicolaou method. The smear was evaluated based on the grading system described by Robinson [5] [Table 1], which takes into account six parameters. A value between one and three was given to every factor analyzed. Scores for each of the six cytologic features were added together to give a total score for each case. In each case the final score ranged between six and 18. Surgical paraffin sections (mastectomy specimen + axillary lymph nodes) were obtained according to routine procedures, and all were given a histologic diagnosis of invasive ductal carcinoma not otherwise specified. Histological samples were evaluated based on the histologic grade according to Elston's modification of the Bloom-Richardson system [8] using 0.45 mm diameter of microscopic field. Three parameters were taken into consideration: degree of tubule formation, nuclear pleomorphism and number of mitoses. Each parameter was scored between one and three. Thus the overall score for all cases ranged between three and nine. Statistical analysis was done employing 'z' test and χ2 test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases were also evaluated for presence or absence of metastasis to the regional lymph nodes employing χ2 test.


   Results Top


Using aspirate samples, cases were cytologically graded according to Robinson categories, with the following results: grade I - 13 cases, grade II - 18 cases and grade III - 12 cases. Using histologic samples, 14 cases were considered grade I, 17 were grade II and 12 were grade III. [Figure 1],[Figure 2],[Figure 3],[Figure 4] show cytologic features found for Robinson grade I, II and III.

Analysis of the data from [Table 2] showed that concordance rate between grade I tumors in cytology and histology was 92.3%, while for grade II was 83.3% and 91.7% for grade III. The overall sensitivity was 89.1% and specificity was 100%. Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histological grading was insignificant in all the three grade ( p0 > 0.05). Therefore, it can be stated that cytologic grading is comparable to histologic grading of tumors to assess the tumor behavior and prognosis, and needs to be evaluated further for its usefulness as a preoperative predictor, especially in cases undergoing chemotherapy.

Multiple regression analysis of the various cytological features with histological scores [Table 3] showed that cell dissociation, nucleoli and chromatin pattern were the most specific parameters ( p0 < 0.001), in determining grades of tumor, followed by other parameters, e.g., cell size ( P < 0.05), nuclear margin (P < 0.05) and cell uniformity ( P < 0.01).

[Table 4] shows results of applying regression analysis to the three histologic features with histological score of the tumor. It was observed that tubule formation and nuclear pleomorphism were better parameters to predict the grade of the tumor ( P < 0.001) as compared to the mitotic count ( P < 0.01).

[Table 5] shows an assessment of the lymph node status data utilizing χ2 test for the various tumor grades in 22 (51.2%) of 43 cytohistologic-graded tumors. Analysis of this data showed lymph node metastasis in 15.4% of grade I, 55.6% grade II and 83.3% of grade III tumors. Statistically significant difference in incidence of lymph node metastasis was noted between grade I and II ( P < 0.01) and grade I and III tumors ( P < 0.001), while difference was insignificant (P > 0.05) between grade II and III indicating a significant increase in lymph node metastasis with increasing cytologic grade from grade I to III tumors.


   Discussion Top


A number of studies have confirmed the prognostic value of histologic grade in invasive ductal breast CA. [9],[10] Fine-needle aspiration cytologic studies have developed a number of scoring systems, with results similar to those obtained from histologic sections, [11],[12] thus confirming the value of FNAC for predicting the histologic grade of a certain tumor preoperatively and therefore its eventual biologic behavior. The purpose of cyto-prognostic grading is to identify fast growing tumors (Grade III), which are more likely to respond to chemotherapy than the low grade; slow growing tumors may be better suited to pretreatment with Tamoxifen. In this study, the histologic grade correlated well with cytologic grade (overall sensitivity 89.1% and specificity 100%). The high value of coefficient of correlation showed a significant and marked association ( P < 0.001) between grades assigned to cytologic and histologic specimens, similar to Taniguchi et al , [6] Chhabra et al, [13] and Bhargava et al . [14]

Multiple regression analysis of cytologic features was used to assess the significance of each cytologic parameter. Coefficients of regression for the following parameters i.e., cell dissociation, nucleoli and chromatin pattern were 0.780, 0.461 and 0.584, respectively, and were statistically significant [Table 4]. For these three parameters, p0 -values were p0 <0.001, therefore, these three parameters were the most influential features, a finding in accordance with studies conducted by Robinson et al, [5] and Chhabra et al . [13] The degree of cell dissociation is an indicator of cell cohesion status and, to an extent, of the degree of expression of the E-cadherin/catenin complex. [15] Loss of cell cohesion appears to facilitate vascular infiltration by tumor cells, which produces an increased incidence of regional lymph node metastasis. A number of studies have shown that neoplasms with greater cell dissociation (and thus cytologic grade II and III) show a higher incidence of regional lymph node metastasis. [16],[17] Robles-Frias et al , [18] also found a statistically significant association between cytologic and histologic grades ( P < 0.0005) and between cytologic grade and presence of axillary metastasis ( p0 < 0.0005). In their further study Robles-Frias et al , [19] found a statistically significant correlation between E-Cadherin/Catenin expression and cytologic grade ( p0 < 0.0005) and this association was particularly relevant to cell dissociation parameter ( p0 <0.0005). Similar results were observed here, testifying to the striking potential of this correlation.

Thus, it is concluded that assigning a cytologic grade in breast carcinoma aspirates done with little effort is reproducible and with rare exceptions, depending on sample limitations, correlates precisely with the histologic grade and permits determination of the aggressiveness of a breast carcinoma. It is a useful parameter to be taken into consideration when selecting mode of therapy for breast carcinoma and to predict the tumor behavior.

 
   References Top

1.Fisher E. The impact of pathology on the biologic, diagnostic, prognostic and therapeutic considerations in breast cancer. Surg Clin North Am 1984;64:361-6.  Back to cited text no. 1    
2.Sunderland MC, McGuire WL. Prognostic indicators in invasive breast cancer. Surg Clin North Am 1990;70:989-1004.  Back to cited text no. 2  [PUBMED]  
3.Elston C, Ellis I. Pathological prognostic factors in breast cancer: I, The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 1991;19:403-10.  Back to cited text no. 3    
4.Haerslev T, Jacobsen GK, Zedeler K. Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immunohistopathological parameters and prognosis in primary breast carcinomas. Breast Cancer Res Treat 1996;37:101-13.  Back to cited text no. 4  [PUBMED]  
5.Robinson IA, McKee G. Cytological grading of breast carcinoma. Acta Cytol 1995;39:1257.  Back to cited text no. 5    
6.Taniguchi E, Yang Q, Tang W, Nakamura Y, Shan L, Nakamura M, et al . Cytological grading of invasive breast carcinoma: Correlation with clinicopathologic variables and predictive value of nodal metastasis. Acta Cytol 2000;44:587-91.  Back to cited text no. 6  [PUBMED]  
7.Richards M, Smith I, Dixon J. Role of systemic treatment for primary operable breast cancer. BMJ 1994;1363-6.  Back to cited text no. 7    
8.Robinson IA, McKee G, Nicholson A, D'Arcy J, Jackson PA, Cook MG, et al . Prognostic value of cytological grading of fine-needle aspirates from breast carcinomas. Lancet 1994;343:947-9.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Latinovie L, Heinze G, Birner P, Samonigy H, Hausmaninger H, Kubista E, et al . Prognostic relevance of three histological grading methods in breast cancer. Int J Oncol 2001;19:1271-7.  Back to cited text no. 9    
10.Simpson JF, Gray R, Dressler LG, Cobau CD, Falkson CI, Gilchrist KW, et al . Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: Results from the Eastern Cooperative Oncology Group Comparison Study EST 4189. J Clin Oncol 2000;18:2059-69.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Skrbinc B, Babic A, Cufer T, Us-Krasovec M. Cytological grading of breast cancer in Giemsa-stained fine needle aspiration smears. Cytopathology 2001;12:15-25.  Back to cited text no. 11    
12.McKee G. Cytologic grading of breast carcinoma. Acta Cytol 2001;39:658-9.  Back to cited text no. 12    
13.Chhabra S, Singh PK, Agarwal A, Bhagoliwal A, Singh SN. Cytological grading of breast carcinoma: A multivariate regression analysis. J Cytol 2005;22:2.  Back to cited text no. 13    
14.Bhargava V, Jain M, Agarwal K, Thomas S, Singh S. Critical appraisal of cytological nuclear grading in carcinoma of the breast and its correlation with ER/PR expression. J Cytol 2008;25:58-61.  Back to cited text no. 14    Medknow Journal
15.Yoshida R, Kimura N, Harada Y, Ohuchi N. The loss of E-cadherin, alpha-and beta-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer. Int J Oncol 2001;18:513-20.  Back to cited text no. 15  [PUBMED]  
16.Yu GH, Cajulis RS, De Frias DV. Tumor cell (dys) cohesion as a prognostic factor in aspirate smears of breast carcinoma. Am J Clin Pathol 1998;109:315-9.  Back to cited text no. 16  [PUBMED]  
17.Yu GH, Lawton TJ, Pasha TL, Reynolds C. Intercellular adhesion molecule expression in ductal carcinoma of the breast: Correlation of immunohistochemical staining with cytologic smear pattern. Diagn Cytopathol 2000;23:73-6.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Robles-Frias A, Gonzalez-Campora R, Martinez-Parra D, Robles-Frias MJ. Vazquez-Cerezuela T, Otal-Salaverri C, et al . Robinson cytologic grading of invasive ductal breast carcinoma: Correlation with histologic grading and regional lymph node metastasis. Acta Cytol 2005;49:149-53.  Back to cited text no. 18    
19.Robles-Frias A, Gonzalez-Campora R, Martinez-Parra D, Robles-Frias MJ, Vazquez-Cerezuela T, Otal-Salaverri C, et al. Robinson cytologic grading in invasive ductal carcinoma of the breast: Correlation with E-cadherin and α-, β and γ-catenin expression and regional lymph node metastasis. Acta Cytol 2006;50:151-7.  Back to cited text no. 19    

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Correspondence Address:
Nazoora Khan
A-11, Medical Colony, Aligarh - 202 002, UP
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.55224

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    Figures

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

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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