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Abstract
Breast carcinoma represents the first female cancer worldwide and the major cause of death among women in the United States. In Egypt, it constitutes 17% of registered cancer in the National Cancer Institute and 21% of all the Egyptian population. The outcome of breast carcinoma can be predicted by conventional and biological prognostic factors. Therefore we undertake this point of research in the Egyptian breast carcinoma to understand the importance of TSP-1 expression in breast carcinoma and to correlate such expression with conventional prognostic factors.
This study included the archival formalin-fixed paraffin embedded blocks of the breast carcinoma specimen, received in the Pathology Laboratory of the Suez Canal University Teaching Hospital in the period between January 2001 to December 2002. Thrombospondin-1 was visualized in tissue sections using ready to use prediluted anti-thrombospondin-1 antibody and the streptavidin biotin detection kit. from each paraffin block, two 5 µm thick sections were obtained, each on a separate slide:
1- One to be routinely stained with H&E. 2- The other section was mounted on positive charged slides to be stained for thrombospondin-1.
In this study there were 47 cases of breast carcinoma, 27 modified radical mastectomies and 27 simple mastectomies. The age ranged from 26 to 73 years, the mean age for all cases was 50.1+10.4.
The 47 cases included in the study comprised cases of 3 DCIS, 32 IDC, 9 ILC, 2 Mucinous carcinoma and one Squamous cell carcinoma.
The 41cases of IDC and ILC were graded according to the Modified SBR grading system, into 10 grade I, 29 grade II and 2 grade III. As for tumor size, 3 of cases were T0, 4 were TI, 24 were T2, 10 were T3 and 6 were T4.
Of the 26 modified radical mastectomies, 6 showed no nodal metastasis, 8 had up to 3 nodal involvement and 12 showed metastatic deposits in more than 3 LNs. The relationship between the histological type of the tumor and number of involved nodes was found to be statistically insignificant. Similarly, the relation between tumor size and nodal status was found to be statistically insignificant.
The intensity of cytoplasmic staining varied from mild to strong and was scored accordingly. The staining intensity of most the IDC cases were moderate. This finding is statistically significant p< 0.001. TSP-1 staining was confined in the cytoplasm in 79% of the cases, while nuclear and cytoplasmic staining was seen in 21%. The pattern of staining in different histological type was statistically insignificant.
There was statistical significant relation between TSP-1staining intensity status and tumor size (p<0.02). But there was statistical insignificant relation between TSP-1staining patterns to various tumor sizes.
The relation of TSP-1 staining intensity status to histological grade in cases of IDC (NOS) of the breast, and with ILC was found statistically insignificant. The relationship of TSP-1 staining pattern status to the modified SBR grading of IDC (NOS) and ILC cases of the breast found to be statistically insignificant.
Looking for the relation between the nodal status and TSP-1 immunostaining, no statistical significant has been found for both the intensity and pattern of staining. Likewise, there was no statistical significance between TSP-1 immunostaining and the mitotic activity.
Conclusion and Recommendation
from the study we conclude the following:
- Angiogenesis is essential for tumor growth metastasis and tumor aggressiveness, thus angiogenic tumors should have a poor prognosis.
- Neovascularization is an early phenomenon in breast neoplasia and is apparent as early as the in situ stage.
- The rule of thrombospondin-1as an anti-angiogenic factor is very interesting in inhibiting tumor cell adhesion, proliferation, motility, and invasion.
- The immunohistochemical detection of thrombospondin-1 has been demonstrated to be reliable, easily performed and widely available technique applied for paraffin embedded tumor specimens.
- Our findings provide evidence that TSP-1 expression can serve as an indicator representing less aggressive potential and favorable prognosis in breast cancer.
- A variety of angiogenic factors are produced by ductal carcinoma in situ, which are variously associated with changes in vascularity, and may facilitate the transition to invasive carcinoma.
- The development of specific anti-angiogenic regimens may provide an alternative to current treatment protocols for breast cancer.