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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 241-244

Correlation of diffusion weighted apparent diffusion coefficient values with immunochemical prognostic factors of breast carcinoma


1 Department of Radiodiagnosis, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of General Surgery, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Surgical Oncology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
4 Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission28-Mar-2020
Date of Acceptance20-Apr-2020
Date of Web Publication6-Jan-2021

Correspondence Address:
Dr. Vijayalakshmi Devi Bodagala
Professor, Department of Radiodiagnosis, SVIMS, Tirupati - 517507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_44_20

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  Abstract 


Context: Classic prognostic markers in breast cancer are tumor size and grade, lymph node status, molecular markers, including estrogen receptor (ER), progesterone receptor (PR), Ki-67 index, human growth factor receptor 2 (HER2) protein, and angiogenic molecular markers. Purpose of present study is to assess the utility of apparent diffusion coefficient (ADC) values in the prognosis of breast cancer by correlating them with molecular biomarkers.
Aim: To correlate the ADC values of DWI of Breast cancer with immunochemical prognostic factors.
Settings and Design: Retrospective observational study.
Materials and Methods: Ours is a retrospective study of 30 female cases of histologically proven breast carcinoma who underwent magnetic resonance imaging (MRI) of breast in Tertiary healthcare centre, Andhra Pradesh. Molecular prognostic factors data were available for 20 cases which were further analyzed.
Statistical Analysis Used: Correlation between the ADC value of the breast tumour and molecular prognostic markers was analyzed using Student's t test.
Results: Mean ADC of Ki-67 index positive cancers (0.755 × 10 - 3 ± 0.158 × 10 - 3mm2/s) was significantly lower than Ki-67 index negative cancers (0.929 × 10-3 ± 0.117 × 10 - 3mm2/s) suggesting statistically significant correlation between ADC value and Ki67 index. There is no significant correlation between ADC value and ER, PR, and HER2 expression status.
Conclusion: Our study showed statistically significant association between ADC values and Ki-67 index. Thus ADC values may be of use in providing prognostic information about disease.

Keywords: Apparent diffusion coefficient (ADC), breast carcinoma, diffusion weighted imaging (DWI), estrogen receptor (ER), progesterone receptor (PR), Ki-67 Index, HER2 receptor


How to cite this article:
Settem T, Bodagala VD, Kishore K H, Kale PK, Lakshmi A Y, Yootla M, Hulikal N, Nandyala R. Correlation of diffusion weighted apparent diffusion coefficient values with immunochemical prognostic factors of breast carcinoma. J NTR Univ Health Sci 2020;9:241-4

How to cite this URL:
Settem T, Bodagala VD, Kishore K H, Kale PK, Lakshmi A Y, Yootla M, Hulikal N, Nandyala R. Correlation of diffusion weighted apparent diffusion coefficient values with immunochemical prognostic factors of breast carcinoma. J NTR Univ Health Sci [serial online] 2020 [cited 2021 Jan 18];9:241-4. Available from: https://www.jdrntruhs.org/text.asp?2020/9/4/241/306124




  Introduction Top


Diffusion-weighted MRI (DWI) has recently been integrated into the standard breast magnetic resonance imaging (MRI) for discrimination of benign and malignant breast lesions.[1]The usefulness of DWI and the apparent diffusion coefficient (ADC) value for the evaluation of primary breast lesions and axillary lymph node Involvement have been researched in many studies.[2] However, there are only few reports documenting the relationship between the ADC values of primary breast lesions and the prognostic factors.[3] Estrogen and progesterone receptors are intracellular steroid hormone receptor proteins which have been used as indicators of prognosis and as a guide to hormone and endocrine therapy.[1] Ki67 index appearing during proliferative phase represents tumor proliferation and significant correlation with high mitotic counts.[4] Human growth factor receptor 2 (HER2) expression had a more malignant phenotype accompanied by cell proliferation, invasion and metastasis.[5] In this retrospective study we have planned to examine the relationship between the mean ADC value of breast cancer with that of molecular prognostic factors.


  Materials and Methods Top


Ours is a retrospective study of 30 female cases of histologically proven breast carcinoma who underwent MRI of breast in a Tertiary Healthcare centre, Andhra Pradesh. Whole medical records are studied to obtain demographic, relevant clinical, laboratory, pathological and imaging data. In total 20 out of 30 cases with molecular prognostic values were further analyzed. The status of estrogen receptor (ER) and progesterone receptor (PR) was considered to be negative if expression was <10% and positive if expression was >10%. Results for HER2 expression were scored as negative, 1+, 2+ or 3+, according to the manufacturer's recommendations. Tumors with 0 or 1+ were classified as HER2 negative and 2+ or 3+ were HER2 positive. Ki-67 staining of >20% was considered positive expression and <20% was considered negative expression. ADC analysis was done by manually placing a ROI with a diameter of 5-10 mm2 on area of high signal intensity on DWI images. The ADC value was automatically calculated in the region of interest. Three measurements where the ADC value was shown to be lower were selected on the ADC map, and were averaged and used as the ADC value. The data were analyzed on excel sheet using Student's t-test

Ethical committee clearance:

As the study was retrospective , there are no ethical issues involved.

Ethical Clearance

Ethical approval for this study (Ethical Committee IEC NO.1046) was provided by the Ethical Committee SVIMS University, Tirupati, Andhra Pradesh, India on 12 February 2007.


  Results Top


Among the 30 female cases who underwent MRI of breast, molecular prognostic factors data were available for 20 cases and mean ADC values are correlated with molecular prognostic factors in these 20 cases. [Table 1] shows correlation between mean ADC values and ER, PR, HER-2, and Ki-67 index positive and negative groups. Mean ADC of Ki-67 index positive cancers (0.755 × 10-3 ± 0.158 × 10-3mm2/s) was significantly lower than Ki-67 index negative cancers (0.929 × 10-3 ± 0.117 × 10-3mm2/s). Significantly lower ADC value is seen in Ki-67 index positive breast cancer, as shown in [Figure 1]. Mean ADC of ER positive cancers (0.776 × 10-3 ± 0.169 × 10-3mm2/s) was not significantly lower than ER negative cancers (0.864 × 10-3 ± 0.159 × 10-3mm2/s). Mean ADC of PR positive cancers (0.786 × 10-3 ± 0.159 × 10-3mm2/s) was not significantly lower than PR negative cancers (0.864 × 10-3 ± 0.166 × 10-3mm2/s) as shown in the [Figure 2] and [Figure 3]. Mean ADC of HER2 positive cancers (0.864 × 10-3 ± 0.132 × 10-3mm2/s) was not significantly lower than HER2 negative cancers (0.802 × 10-3 ± 0.192 × 10-3mm2/s).
Table 1: Showing Correlation Between Mean ADC Values and ER, PR, HER-2 and KI-67 Index Positive and Negative Groups

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Figure 1: A 60-year-old woman with infiltrative ductal carcinoma (arrow), Immunohistochemical staining for estrogen receptors and progesterone receptors showed positivity. HER2 gene expression showed positivity. Ki-67 index positivity. (a) STIR image. (b) Diffusion weighted image (b = 800 s/mm2). (c) ADC map(0.656 × 10-3 mm2/s)

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Figure 2: A 66-year-old woman with infiltrative ductal carcinoma (arrow), Immunohistochemical staining for estrogen receptors and progesterone receptors showed positivity. HER2 gene expression showed negativity. Ki-67 index showed a positive increase of over 40%. (a). STIR image (b). Diffusion weighted image (b = 800 s/mm2) (c). ADC map (0.713 × 10-3 mm2/s)

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Figure 3: A 59-year-old woman with infiltrative ductal carcinoma (arrow), Immunohistochemical staining for estrogen receptors and progesterone receptors showed negativity. HER2 gene expression showed negativity. Ki-67 index showed a positive increase of over 50%. (a) STIR image. (b) Diffusion weighted image (b = 800 s/mm2). (c) ADC map (0.750 × 10 - 3 mm2/s)

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  Discussion Top


Several studies have reported that malignant tumors usually show higher signal intensity on DWI, compared with benign lesions and normal fibroglandular tissue, resulting in lower ADC values.[6] The ADC is a quantifiable value that provides a measurement of signal attenuation and is affected by microscopic motion, including molecular diffusion of water and blood microcirculation in the capillary network.[7] Water diffusion is greatly influenced by factors such as cellularity, fluid viscosity, intra- and extracellular membrane permeability, active transport, flow and structural directionality.[8] It has been suggested that the decreased ADC value in malignant tumors may be due to their increased cellularity, larger nuclei with more abundant macromolecular proteins, and less extracellular space.[9]

Estrogen/progesterone receptor status is another major factor that affects the operation procedures and treatment alternatives. In this study, we found no significant correlation between the mean ADC values and the ER and PR status. [Table 2] shows comparison of present study with similar studies in literature.[2],[4],[12]
Table 2: Showing Relationship Between ER, PR Status and ADC Values

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High Ki-67 index is associated with poor prognostic differentiation and with lymph node metastasis.[10] In our study, mean ADC value was significantly lower in cases of Ki-67 index positive cases, compared with negative cases. The result could be an indication that increased Ki-67 index is a marker of increased cellularity and correlated with lower ADC values.

HER2-positive cells have more malignant phenotypes than HER2-negative cells, which is associated with a higher rate of cell proliferation, invasion and metastasis.[5] ADC values of HER2-positive IDC are assumed to be lower than those of HER2 negative IDC owing to increased cellularity. However, Park et al.[11]reported an opposite result and showed significantly higher ADC values in their study involving 110 IDC cases. On the other hand, Kamitani et al.found no correlation between HER2 overexpression and the ADC values of IDC lesions. In our study also there is no significant correlation between these two variables.

Limitations of present study is a single centre study with small sample size.


  Conclusion Top


This study showed statistically significant association between ADC values and Ki-67 values which is a marker of increased cellularity. Thus ADC values may be of use in providing prognostic information about disease.

Financial support and sponsorship

Sri Balaji Arogya Varaprasadini Scheme, SVIMS.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Choi SY, ChangY-W, Park HJ, Kim HJ, Hong SS, SEODY.Correlation of the apparent diffusion coefficiency values on diffusion-weighted imaging with prognostic factors for breast cancer.Br J Radiol2012;85:e474–9.  Back to cited text no. 1
    
2.
Kim SH, Cha ES, Kin HS, Kang BJ, Choi JJ, Jung JH, et al. Diffusion-weighted imaging of breast cancer: Correlation of the apparent diffusion coefficient value with prognostic factors. J Magn Reson Imaging 2009;30:615-20.  Back to cited text no. 2
    
3.
Jeh SK, Kim SH, Kim HS, Kang BJ, Jeong SH, Yim HW, et al. Correlation of the apparent diffusion coefficient value and dynamic magnetic resonance imaging findings with prognostic factors in invasive ductal carcinoma. J Magn Reson Imaging 2011;33:102-9.  Back to cited text no. 3
    
4.
Ding SL, Sheu LF, Yu JC, Yang TL, Chen B, Leu FJ, et al., Expression of estrogen receptor-alpha and Ki67 in relation to pathological and molecular features in early-onset infiltrating ductal carcinoma. J Biomed Sci 2004;11:911-9.  Back to cited text no. 4
    
5.
Woodhams R, Matsunaga K, Iwabuchi K, Kan S, Hata H, Kuranami M, et al. Diffusion-weighted Imaging of malignant breast tumors. J Comput Assist Tomogr 2005;29:644-9.  Back to cited text no. 5
    
6.
Kinoshita T, Yashiro N, Ihara N, Funatu H, Fukuma E, Narita M. Diffusion-weighted half-fourier single-shot turbo spin echo imaging in breast tumors: Differentiation of invasive ductal carcinoma from fibroadenoma. J Comput Assist Tomogr 2002;26:1042-6.  Back to cited text no. 6
    
7.
Partridge SC, Mullins CD, Kurland BF, Allain MD, DeMarini WB, Eby PR, et al. Apparent diffusion coefficient values for discriminating benign and malignant breast MRI lesions: Effects of lesion type and size. AJR Am J Roentgenol 2010;194:1664-73.  Back to cited text no. 7
    
8.
Szabo BK, Aspelin P, Wiberg MK, Tot T, Bone B. Invasive breast cancer: Correlation of dynamic MR features with prognostic factors. Eur Radiol 2003;13:2425-35.  Back to cited text no. 8
    
9.
Guo Y, Cai YQ, Cai ZL, Gau YG, An NY, Ma L, et al. Differentiation of clinical benign and malignant lesions using diffusion-weighted imaging. J Magn Reson Imaging 2002;16:172-8.  Back to cited text no. 9
    
10.
Donegan WL. Tumor-related prognostic factors for breast cancer. CA Cancer J Clin 1997;47:28-51.  Back to cited text no. 10
    
11.
Park MJ, Cha ES, Kang BJ, Ihn YK, Baik JH. The role of diffusion- weighted imaging and the apparent diffusion coefficient (ADC) values for breast tumors. Korean J Radiol 2007;8:390-6.  Back to cited text no. 11
    
12.
Kamitani T, Matsuo Y, Yabuuchi H, Fujita N, Nagao M, Jinnouchi M, et al. Correlations between apparent diffusion coefficient values and prognostic factors of breast cancer. Magn Reson Med Sci. 2013;12:193-9.  Back to cited text no. 12
    


    Figures

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

  [Table 1], [Table 2]



 

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