1. Table 2. Association between histology grade, lymph node status,
CLAUDIN-7 CORRELATES WITH BREAST CARCINOMA HISTOLOGICAL GRADE BUT NOT WITH OUTCOME
E. A. Khramtsova1, V. Macias1, M. K. Patel1, J. Akhtar1, O. Jee3, W. Gao2, W-M. Liang2, C. Beam2, B. Gilks4, E. Wiley1 and A. K. Balla1
1 Department of Pathology, University of Illinois-Chicago, Chicago, IL, USA, 2 Department of Epidemiology and Biostatistics, University of Illinois-Chicago, Chicago, IL, USA, 3 Carleton College, Northfield, MN, USA, 4 Department of Pathology, University of British Columbia, Vancouver, Canada
UIC
UIC
UNIVERSITY OF ILLINOIS AT CHICAGO
UNIVERSITY OF ILLINOIS AT CHICAGO
Table 2. Association between histology grade, lymph node status,
outcomes and claudin -7 score by using Fisher’s exact test
INTRODUCTION
Invasive breast carcinoma is the most common malignancy and is the second most common cause of cancer death in the United States among women. Metastasis is the primary cause of fatality in breast cancer patients. Since claudin-7 serves an important role in both epithelial cell tight junction formation and function, several studies have investigated its utility as a biomarker for breast cancer. Normal breast epithelial cells have strong expression of claudin-7. Previous publications have shown an inverse correlation of claudin-7 immunohistochemical expression and breast cancer histological grade. However, no formal study has been performed to investigate whether claudin-7 immunohistochemical expression can be used as prognostic marker.
This study aims to determine whether claudin-7 expression correlates with breast cancer outcomes.
Variable
Claudin-7 Score %
P-value 1 2 3
Histology grade
0.27
Grade 1
16.67
9.68
5.45
Grade 2
25.00
31.18
47.27
41.67
Grade 3
58.33
59.14
Node status
0.07
Negative
90.00
68.13
51.92
57.14
Positive
10.00
31.87
48.08
42.86
Disease outcome status
0.74
Death of breast
15.38
31.34
26.67
Death from other reasons
23.08
20.37
22.39
33.33
Alive
61.54
54.63
46.27
40.00
Figure 2. View of the ImageScope viewer (Aperio ScanScope) shows TMA cores with immunohistochemical staining of Claudin-7
MATERIALS AND METHODS
Breast tissues for TMA construction were obtained from the Department of Surgical Pathology archive at the Vancouver General Hospital with local ethical committee approval. The samples were de-identified and data used under anonymous numbers.
TMA was generated using Tissue Arrayer®.
Immunohistochemical staining on TMA slides was performed with rabbit anti-claudin-7 antibody (Zymed).
Pathologist-based semiquantitative analysis was determined by evaluating the intensity of the membrane reaction for claudin-7 with the HercepTest criteria.
Automated image analysis performed by HercepTest algorithm with TMALab software (Aperio ScanScope).
Interpretation of claudin-7 expression (staining intensity criteria)
Score: 0 Staining Pattern :No staining is observed or membrane staining is observed in less than % of the tumor cells .
Score: 1+ Staining Pattern: A faint/barely perceptible membrane staining is detected in more than 10% of the tumor cells. The cells are only stained in part of their membrane.
Score: 2+ Staining Pattern: A weak to moderate complete membrane staining is observed in more than 10% of the tumor cells.
Score: 3+ Staining Pattern: A strong complete membrane staining is observed in more than 10% of the tumor cells.
Table 3. Test association between tumor size and claudin -7 score
Variable
Mean±STD
P-value
Claudin-7 Score 1 2 3
Tumor size
3.42±2.78
2.74±1.91
3.35±3.50
2.41±1.04
0.36
RESULTS
Table 1. Descriptive statistics for categorical variables ( total sample size=207)
CONCLUSIONS
There is no statistical correlation between the digital image score analysis of claudin-7 and outcomes and between claudin-7 and any of the other parameters (stage, grade, and positive lymph node).
Variable N %
Claudin-7 Immunohistochemistry Score 14
6.76 1
110
53.14 2 68
32.85 3 15
7.25
Histology grade
(missing=35)
Grade 1 16
9.30
Grade 2 63
36.63
Grade 3 93
54.07
Node status
(missing=40)
Negative
106
63.47
Positive 61
36.53
Disease outcome status
(missing=4)
Death of breast cancer 54
26.60
Death from other reasons 45
22.17
Alive
104
51.23
Detail of the previous
image
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Tissue microarray (TMA) block
TMA slides immunostained with anti-claudin-7
Figure 1. Methodology of tissue microarray technology in the evaluation of
claudin-7 expression