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Year : 2009  |  Volume : 52  |  Issue : 2  |  Page : 159-163
Quick score of hormone receptor status of breast carcinoma: Correlation with the other clinicopathological prognostic parameters


Department of Pathology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka

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   Abstract 

Background: Immunohistochemical assessment of the hormone receptor status of breast carcinoma is a routine investigation. However, there is no worldwide consensus on the scoring system. The Quick Score is claimed to be a reliable scoring system, which assesses both the proportion of stained cells and the intensity of staining. Aims: To assess the value of Quick Score in terms of accepted clinicopathological parameters and to document the prevalence of hormone receptor-positive breast carcinomas in the study sample. Materials and Methods: Clinicopathological parameters of 151 breast cancers were compared with the Quick Scores for estrogen receptor (ER) and progesterone receptor (PR) status. Results and Conclusions: The Quick Score for ER was 0 in 54.3% (82/151) and for PR was 0 in 51.7% (75/145), indicating no hormone receptor expression in the majority. The Nottingham grade and the mitotic count had a significant inverse relationship with the Quick Score for hormone receptor status. The Nottingham Prognostic Index (NPI) also had an inverse relationship with the hormone receptor status.

Keywords: Breast carcinoma, hormone receptor status, Quick score

How to cite this article:
Mudduwa LK. Quick score of hormone receptor status of breast carcinoma: Correlation with the other clinicopathological prognostic parameters. Indian J Pathol Microbiol 2009;52:159-63

How to cite this URL:
Mudduwa LK. Quick score of hormone receptor status of breast carcinoma: Correlation with the other clinicopathological prognostic parameters. Indian J Pathol Microbiol [serial online] 2009 [cited 2014 Sep 2];52:159-63. Available from: http://www.ijpmonline.org/text.asp?2009/52/2/159/48906



   Introduction Top


Immunohistochemical evaluation of estrogen receptor (ER) and progesterone receptor (PR) status of breast carcinoma has become a routine investigation to predict the response to endocrine therapy. The presence of ER is related to a favorable response to endocrine therapy and improved overall survival. [1] Unlike the immunohistochemical evaluation of Her 2 status of breast carcinoma, there is no worldwide accepted general agreement on a scoring system for the immunohistochemical evaluation of hormone receptor status of breast carcinoma. The two main features evaluated are the proportion of stained cells and the intensity of the staining. There are several different methods to evaluate these two features: Quick Score, H score, Allred score and the proportion of positive cells. [1],[2]

In Sri Lanka, it is the proportion of stained cells that is assessed to express the hormone receptor status. However, some pathologists take the intensity of staining as well into account, although it is not expressed as a score. Our institution uses the Quick Score to express the hormone receptor status as in the United Kingdom. [3]

The present study intended to evaluate the value of the Quick Score in terms of the correlation with the other proven clinicopathological prognostic parameters of breast carcinoma and to document the prevalence of hormone receptor-positive breast carcinomas in our population.


   Materials and Methods Top


This descriptive study was carried out in our institution. Our department is the only center in the province that provides immunohistochemistry diagnostic facility. Therefore, we receive wax blocks of breast carcinomas for ER, PR and Her 2 assessment from almost all breast cancer patients in the province. All breast cancers that had ER, PR and Her 2 status reported by the author from June 2006 to July 2008 were included in the study. The author had been on the reporting roster every fortnight to report on all the invasive breast cancer cases referred for immunohistochemical assessment of prognostic markers during the 2-week slots. Specimens reported by the others were excluded to eliminate interobserver variation in assigning a score.

One 4- section from each submitted paraffin block was stained with hematoxylin and eosin to verify the presence of invasive breast carcinoma and adequacy of fixation. From the selected blocks, 4--thick sections were taken onto poly-L-Lysine-coated slides. Immunostainings were performed using the Streptavidin Biotin method. Dako polyclonal rabbit antihuman progesterone receptor (A0098), polyclonal rabbit antihuman c-erbB-2 oncoprotein (M7047), monoclonal mouse antihuman ER α, clone 1D5 (M704701) and Universal LSAB2 kit/HRP rabbit/mouse with streptavidin/HRP (K0675) were used for immunohistochemical staining, which was carried out manually by an experienced technical officer. Evaluation of the staining and assigning a score were performed by the author. The staining was evaluated on the invasive component only. Best-preserved and best-stained areas of the sections were assessed. Nuclear staining was assessed for ER and PR while membrane staining was assessed for Her 2. A score for the proportion of stained cells (0 = no nuclear staining, 1 = <1% nuclear staining, 2 = 1-10% nuclear staining, 3 = 11-33% nuclear staining, 4 = 34-66% nuclear staining and 5 = 67-100% nuclear staining) and the intensity of staining (0 = no staining, 1 = weak staining, 2 = moderate staining, 3 = strong staining) were assigned to each tumour. The score for the proportion of cells stained and the score for the intensity of staining were added to get the total score, which ranged from 0 to 8 [Figure 1] and [Figure 2]. However, a score of 1 was not given as the overall Quick Score is the sum of two scores. The author adhered to the guidelines given by the United Kingdom National Health Service Breast Screening Programme in assigning scores. [2],[3] The immunohistochemical staining for Her 2 was scored according to the guidelines published by Ellis et al. [4] Tumors that showed strong complete membranestaining in >10% of the tumour cells were considered positive [Figure 3].

The tumor grade was assessed by the author on the hematoxylin and eosin-stained slides using the Nottingham Grading System. [5] Data on the size of the tumor and the lymph node status were obtained from the histopathology reports of the breast carcinoma. The NPI was calculated for each tumor [NPI = 0.2 tumor size in cm + lymph node status (1, 2, 3) + histological grade (1, 2, 3)]. [3]

For the statistical analysis, the size of the tumor was categorized into three groups (<2cm, 2-5cm and >5cm) as it signifies three different stages in the TNM Staging system. [6] The NPI was also categorized into three prognostic groups (<3.4, 3.4-5.4, >5.4) according to the prognostic groups stated in the guidelines given by the United Kingdom National Health Service Breast Screening Programme. [3] Age was compared with the ER and PR scores to assess whether there is any difference between the breast cancers in young women and the rest (<40 years and ≥40 years).

The Pearson χ2 test was used to compare the Quick Score with the tumor characteristics: Her 2 status, grade, lymph node status, size, NPI and the age of the patient. Statistical analysis was performed using the SPSS version 11.

This study was conducted after obtaining the ethical approval from the Ethical Review Committee of our institution.


   Results Top


A total of 151 breast carcinomas were included in the study. This included wax blocks from 115 mastectomy, 23 lumpectomy and 13 Tru cut biopsy specimens. The age of the subjects enrolled ranged from 31 to 85 years, with a mean of 52.5 years (SD 11.95). The group of young women with breast cancer (<40years) included 21 patients (14.3%).

The size of the tumor ranged from 0.2 to 14.2cm, with a mean size of 3.52cm (SD 2.34). The tumor measured >5cm in maximum diameter in 11.5% (15/131) of the patients while the majority 74% (97/131) had tumors measuring 2-5cm in the maximum dimension. The tumor size was <2cm in 14.5% (15/131) of the patients. The size of the tumor was not available for 20 patients. This included all Tru cut biopsies and seven lumpectomy samples. For 16 patients who had lumpectomy initially, the lymph node status was available by the time they were referred for prognostic maker assessment as mastectomy had followed the lumpectomy soon after the diagnosis.

The lymph node status was available for only 111 patients as information on the lymph node involvement was not available for 40. This included all Tru cut biopsies and some lumpectomy and mastectomy specimens. The histopathology reports of these tumors did not indicate the lymph node status. A large proportion of patients 42.3%(47/111) was pNO as they did not have any lymph node metastasis. More than 50% had lymph node metastasis and 27.9% (31/111) were pN1 while 29.7% (33/110) were pN2.

The histological grade was assessed in all 151 cases. A little less than half of the sample, 49% (74/151) was grade 3 tumors while 36.4% (55/151) and 14.6% (22/151) were grade 2 and 1, respectively.

The NPI could be calculated only for 110 patients, which ranged from 2.2 to 7.4 (mean 4.86, SD 1.35). 47.3% (52/110) of the patients were in the group of NPI between 3.4 and 5.4. The NPI was more than 5.4 in 37.3% (41/110) and <3.4 in 17/96 (15.5%) of the patients. The NPI could not be calculated for 41 patients as either lymph node status or size of the tumor or both were not available in the patients' histopathology report.

The three immunohistochemical parameters, ER, PR and Her 2 status were not available for all 151 patients included in the study as the immunomarkers were performed on the request of the clinician and for some patients the clinicians had not requested all three markers. The Quick Score of ER for all 151 breast carcinomas and PR for 145 breast carcinomas was available for evaluation [Table 1]. The Quick Score for ER was 0 in 54.3% (82/151) and PR was 0 in 51.7% (75/145), indicating no hormone receptor expression in the majority. [Table 1] shows the Quick Score distribution for ER and PR in the study population.

Her 2 was positive in 26/136 (19.1%) of the tumors. There were only three tumors with borderline expression, which were considered negative for this study. A majority of the Her 2-positive tumors had no hormone receptor expression (69.2% were ER negative and 61.53% were PR negative).

The grade was inversely related to the overall Quick Scores of both ER and PR expression (ER P < 0.001 and PR P = 0.001). Both components of the Quick Score, proportion of stained cells and intensity of staining also had a statistically significant inverse relationship with the grade. This was true for both ER and PR ( P < 0.0001 for ER and P = 0.001 for PR).

The Quick Scores for both ER and PR were analyzed against the score given for the three components of the Nottingham grade: nuclear pleomorphism, tubule formation and mitotic count. Nuclear pleomorphism and mitotic count had a statistically significant correlation with the Quick Scores for ER ( P = 0.005 and < 0.0001, respectively). The strength of correlation was highest with the mitotic count. Both components of the Quick Score, percentage of cells and intensity of staining, had a significant correlation with nuclear pleomorphism and mitotic count [Table 2]. But, PR had a significant correlation only with the mitotic count ( P < 0.0001). Similar to the grade, they were negatively correlated with the hormone receptor status, expressed as the Quick Score.

Of all the other parameters assessed, only the Her 2 status and the NPI had a correlation with the Quick Score. The overall Quick Score for ER had a statistically significant correlation with the NPI. The score for the intensity of staining for PR was significantly correlated with the Her 2 expression and the NPI. Age, size of the tumor and lymph node status had no statistically significant correlation with the overall Quick Score for ER and PR. There was no statistically significant difference between the breast carcinoma in young women and the rest with regard to the ER and PR expression or other prognostic parameters considered in the study.

When the overall score of 2 or more considered the positive hormone receptor expression, both grade and NPI had a negative correlation with the hormone receptor status, which was statistically significant [Table 3].


   Discussion Top


The hormone receptor status of breast carcinoma can predict the response to adjuvant endocrine therapy. The prevalence of hormone receptor-positive breast cancer in Asian countries has been found to be lower than the western world where more than 50% tumors express hormone receptors. Christopher et al. [7] have documented a prevalence of 76-78% of hormone receptor-positive breast cancers in the United States from 1992 to 1998 with a rise in the prevalence over the years. However, the number of studies performed on this topic is much less in the Asian communities compared with the western world. A prevalence of 32.6% for ER-positive and 46.1% for PR-positive breast cancers has been documented in a study carried out in India. [8] A Jordanian study revealed 50.8% ER-positive tumors and 57.5% of PR-positive tumors in their study sample. [9] The present study documents a prevalence of 54.3% for completely negative ER and 51.7% for completely negative PR. Therefore, only a 45.7% (ER) and a 48.3% (PR) of tumors express hormone receptors when the Quick Score of 2 or more is considered positive. It indicates that the majority of the breast carcinomas in the study sample would not respond to endocrine therapy. However, the Her 2 overexpression is comparable with the rest of the world.

The majority of patients included in the present study had high-grade tumors, which explains the low prevalence of hormone receptor expression. It is often observed that high-grade tumors tend to be negative for hormone receptor expression. The present study shows that the Quick Score inversely correlates with the Nottingham grade of the tumor, which is statistically significant. The component of the Nottingham grade, which correlates well with the Quick score for both ER and PR, was the mitotic count. The mitotic count of a tumor expresses its proliferation capacity, which has been identified as a good prognostic factor. There are a few studies performed on the usefulness of the proliferative activity of the tumor and the predictive value for responsiveness to adjuvant therapy. However, the results are somewhat conflicting. [10] Jirstrom et al. [10] found a significant difference in the recurrence-free survival following treatment with tamoxifen in a population with high mitotic activity. Recurrence-free survival had been significantly improved for grade 2 and 3 tumors in their study sample. They also described that the beneficial effect of tamoxifen was significant in highly proliferating tumors, both in terms of recurrence-free survival and in terms of breast carcinoma survival, suggesting an important role for tamoxifen in this group of tumors. [10]

In the present study, the overall grade of the tumor correlated well not only with the proportion of cells stained but also the intensity of staining, the two components of the Quick Score that justify the assessment of the intensity of staining in giving a score.

The NPI was between 3.4 and 5.4 in the majority. The NPI correlated well with the hormone receptor status when the cut-off point is 2. An overall Quick Score of 2 indicates that there is weak staining in <1% of the tumor cells.

The majority of patients included in the present study had lymph node metastasis by the time they sought treatment. The majority (74%) presented with a size between 2 and 5cm. Hence, the majority do not present in the early stage. This may be due to the absence of a national breast screening carried out in Sri Lanka.

The proportion of stained cells, Allred score, Quick Score and H score are the most commonly used methods to assess the hormone receptor status in most research publications on the subject. The cut-off point corresponding to 10% of the stained cells has been used to identify the hormone receptor-positive tumors. [1],[10],[12] It has been found that there is a significant association between the proportion of cells stained and the response to endocrine therapy. [1],[10],[12] A significant difference in the 5-year recurrence-free survival has been seen between ER-positive and ER-negative patients for a cut-off of 10% and overall and 5-year survival for a cut-off of 33%. [12]

The same study found a significant difference in the overall and 5-year survival for a cut-off in the total Allred score between 4 and 5. [12]

With the Quick Score, a score above 2 (above 1% of weakly positive cells) has been reported to predict responsiveness to endocrine treatment. [11] When a Quick Score of >2 was taken as the cut-off, only 35% of the tumors in the present study population were ER positive while 39.9% were PR negative. This is a remarkable deviation from the western figures. However, Yamashita et al. [1] suggested the cut-off to be set low for metastatic disease as they may respond to endocrine therapy even with low hormone receptor expression. As most published data have come from response to metastatic disease, it is difficult to define cut-off points that are applicable to adjuvant setting. [3]

The European Working Group for Breast Screening Pathology [11] found that there was a poor concordance between observers in assigning a score to tumors except in very strongly positive or completely negative tumors. Therefore, a Quick score of 0 and 7-8 can be relied upon for therapy. The same study concluded that technical and interpretive variations were responsible for the variation in the assessment of the Quick Score in low and moderate levels of hormone receptor expression. [11]

A significant proportion of the present study sample (19.8% for ER and 18.6% for PR) expressed low levels of receptors according to the subcategories suggested by the European Working Group for Breast Screening Pathology [11] (Quick Score 2-4). The Quick Score of this group of tumors could have probably been subjected to variation. Therefore, inclusion of a weakly positive control to the routine staining procedure is suggested to reduce the technical variation. Because the author had strictly adhered to the guidelines given by the United Kingdom National Health Service Breast Screening Programme in assigning a score, interpretative variation was expected to be minimal in this study. Interobserver variation was eliminated at the beginning.


   Conclusions Top


The prevalence of hormone receptor-positive breast cancers is less in the study population of Asian women compared with the western world even with a very low cut-off. This is probably due to the high prevalence of high-grade tumors among the study population. The Nottingham grade and the mitotic count have a significant inverse correlation with the Quick Score of hormone receptor expression. The proportion of stained cells and the intensity of staining correlate well with the Nottingham grade. NPI shows a statistically significant negative correlation with the overall Quick Score.

The present study demonstrates a good correlation of the Quick Score of hormone receptor status with some of the well-established pathological parameters of breast carcinoma. It justifies the use of Quick Score in assessing the hormone receptor status.


   Acknowledgements Top


Mrs. GGDD Gunawardhane of the Department of Pathology, Faculty of Medicine, University of Ruhuna, Sri Lanka, is acknowledged for the technical assistance provided by staining all the slides.

 
   References Top

1.Yamashita H, Ando Y, Nishio M, Zhang Z, Hamaguchi M, Mita K, et al . Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer. Breast Cancer 2006;13:74-83.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Leake R, Barnes D, Pinder S, Ellis I, Anderson L, Anderson T, et al . Immunohistochemical detection of steroid receptors in breast cancer: A working protocol. J Clin Pathol 2000;53:634-5.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Guidelines Working Group of the National Coordinating Committee for Breast Pathology. Pathology reporting of breast diseases. NHSBSP Publication No. 58 January 2005. p. 86-7.  Back to cited text no. 3    
4.Ellis IO, Bartlett J, Dowsett M, Humphreys S, Jasani B, Miller K, et al . Best Practice No. 176: Updated recommendation for HER2 testing in the UK. J Clin Pathol 2004;57 : 322-7.  Back to cited text no. 4    
5.Elston CW, Ellis IO. Assessment of histological grade. In: Elston CW, Ellis IO, editors. The Breast. Great Britain: Redwood Books Ltd; 2000. p. 365-484.   Back to cited text no. 5    
6. Singletary SE , Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al . Revision of the American Joint Committee on Cancer Staging for breast cancer. J Clin Oncol 2002;20:3628-36.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Li CI, Darling JR, Malone KE. Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol 2003;21:28-34.  Back to cited text no. 7    
8.Desai SB, Moonim MT, Gill AK, Punia RS, Naresh KN, Chinoy RF. Hormone receptor status of breast cancer in India: A study of 798 tumours. Breast 2000;9:267-70.  Back to cited text no. 8    
9.Sughayer MH, Al-Khawaja M, Massarweh S, Al-Masri M. Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan. Pathol Oncol Res 2006;12:83-6.  Back to cited text no. 9    
10.Jirstrom K, Ryden L, Anagnostaki L. Nordenskjold B, Stal O, Thorstension S, et al . Pathology parameters and adjuvant tamoxifen response in a randomized premenopausal breast cancer trial. J Clin Pathol 2005;58:1135-42.  Back to cited text no. 10    
11.Wells CA, Sloane JP, Coleman D, Munt C, Amendoeira I, Apostolikas N, et al . Consistency of staining and reporting of oestrogen receptor immunohistochemistry within the Europian Union: An inter-laboratory study. Virchows Arch 2004;445:119-28.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Horii R, Akiyama F, Ito Y, Iwase T. Assessment of hormone receptor status in breast cancer. Pathol Int 2007;57:784-90.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Lakmini K.B Mudduwa
Department of Pathology, Faculty of Medicine, University of Ruhuna, Galle
Sri Lanka
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DOI: 10.4103/0377-4929.48906

PMID: 19332901

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    Figures

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    Tables

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