الفهرس 
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Abstract
Most diagnoses in breast pathology can be rendered tissue section. However, a significant number of both benign and malignant lesions can show variable morphologic patterns and significant histologic overlap, leading to diagnostic uncertainty. These challenges and complexities have opened the door to an expanding role for immunohistochemistry (IHC) as an important diagnostic adjunct for solving frequently encountered problems in breast pathology. Although IHC has proven to be a powerful tool in helping to resolve difficult cases, the results of such studies should always be carefully interpreted within the morphologic context for each lesion.
The interpretation of immunohistochemistry (IHC) results in breast disease should be grounded upon an understanding of the appropriate circumstances and situations in which certain antibodies should be used diagnostically and an understanding of the limitations of these sorts of assays.
This study was conducted in order to assess the expression of p63 and CK5/6 in benign ductal proliferations and malignant ductal breast lesions in order to determine the role of these markers in differentiating between both lesions. Our study included 50 cases; the benign group (n=25) included 10 cases of intraductal papillomas, 10 cases of usual ductal hyperplasia and 5 cases of atypical ductal hyperplasia. The malignant group (n=25) included 15 cases of duct carcinoma in situ and 10 cases of infiltrating duct carcinoma, not otherwise specified.
Paraffin sections from each block were stained with H&E. Two serial sections from each block were prepared and stained immunohistochemicaly for p63 and CK5/6 monoclonal antibodies.
Positive staining for p63 was seen as nuclear brown staining, which was scored on a scale from 0 to +3 according to the percentage of the total number of stained myoepithelial cells.
p63 immunoexpression varied significantly between benign and malignant cases, being higher in benign cases (p<0.001). p63 immunoexpression showed a statistically significant relation with the histopathologic diagnosis (p<0.001).
A score of +3 was seen in intraductal papilloma and usual ductal hyperplasia cases and a continuous layer of myoepithelial layer was observed. In atypical ductal hyperplasia (60%) and duct carcinoma in situ (60%) cases, a score of +1 was seen. In both subgroups, p63 was observed as a discontinuous layer with focal gaps, being more frequent and exaggerated in duct carcinoma in situ cases. All infiltrating duct carcinoma cases lacked p63 expression.
We did not find a statistically significant difference between atypical ductal hyperplasia and duct carcinoma in situ concerning p63 immunoexpression (p>0.005).
We did not find a significant relation between the grade of DCIS and p63 immunoscore (p-value>0.05).
High statistical significant correlation (inverse) was found between the age and p63 immunoscore (p<0.001).
Positive staining for ck5/6 was seen as cytoplasmic alone and/or along with membranous staining, Ck5/6 immunoscore was obtained by multiplying the staining intensity with percentage positivity, thereby giving immunoscores ranging from 0 to 300.
Ck5/6 immunoscore was significantly higher in the benign group than in the malignant group (p<0.001). Ck5/6 immunoexpression showed a statistically significant relation with the histopathologic diagnosis (p<0.001).
A high to very high immunoscore was seen in most of the cases of intraductal papillomas (90%) and all cases of usual ductal hyperplasia. All cases of atypical ductal hyperplasia and duct carcinoma in situ showed a negative/low immunoscore while all infiltrating duct carcinoma cases lacked ck5/6 expression.
We did not found a significant relation between Ck5/6 score and grade of DCIS (p>0.05).
High statistical significant correlation (inverse) was found between the age and ck5/6 immunoscore (p<0.001).
High statistical significant correlation (direct) was found between p63 immunoscore and Ck5/6 immunoscore in both groups (p<0.001).
We used ROC analysis for determining the cut-off value for each marker in diagnosing malignant breast lesions in our study. For p63 the cut off value was ≤ 50 and for ck5/6 the cut-off value was ≤ 20.
In conclusion, the current study confirmed that benign and malignant ductal breast lesions demonstrated a statistically significant difference in the immunoexpression and patterns for p63 and ck5/6. Our findings suggest that p63 is a sensitive and specific nuclear myoepithelial marker that can be included in immunohistochemical panels aiming in identify myoepithelial cells in problematic breast lesions. Our findings also indicate that ck5/6 can be a useful diagnostic adjunct in differentiating cases with UDH and ADH/DCIS.
Recommendations for future studies:
It is important to use immunohistochemistry carefully and re-evaluation of histological findings on H&E and clinicopathological correlation is mandatory.
For detection of the presence/absence of myoepithelial cells and in differentiating between varies IPLs, it is important not to rely on just one marker. At least 2 markers should be used; one of them should be nuclear.
Double immunostaining technique using separate chromophores for each antibody can be very useful and informative.
Also, it is recommended for further studies to include more subtypes of breast cancer other than infiltrating duct carcinoma, not otherwise specified.
It is also recommended to study the expression of CK14, CK5/6, CK17 and p63 (basal/stem cell markers), in correlation with CK8/18 and CK19 (luminal marker) and other clinicopathological, molecular and immunohistochemical variables for better categorization of ductal hyperplasia of usual and atypical type, DCIS and IDC and this may aid also in interpretation of the wide spectrum of morphological variables of breast tumors.