Expression of sema4d and its receptor Plexin-b1 in invasive breast ductal Carcinoma in relation to Tumor angiogenesis and Tumor-associated macrophages
Cumulative experimental and clinical studies have shown involvement of Sema4D, a Class IV semaphorin, and its receptor, Plexin-Bl in tumor progression. Particularly, regulation of monocytic cells by Sema4D, and tumor angiogenesis via Sema4D/Plexin-B 1 receptor system are of great interest. This s...
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| Format: | Thesis |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | http://eprints.usm.my/60936/1/CHING%20EWE%20SENG%20-%20e.pdf |
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| Summary: | Cumulative experimental and clinical studies have shown
involvement of Sema4D, a Class IV semaphorin, and its receptor, Plexin-Bl in tumor
progression. Particularly, regulation of monocytic cells by Sema4D, and tumor
angiogenesis via Sema4D/Plexin-B 1 receptor system are of great interest. This study
characterized the expressions of Sema4D and Plexin-B 1 in human invasive breast ductal
carcinoma and evaluated their relationships with other pertinent clinicopathological
parameters in general, and with tumor-associated macrophages and tumor angiogenesis
in particular. Expressions of Sema4D and Plexin-Bl in 94 patients diagnosed of
invasive ductal carcinoma, NOS were explored immunohistochemically on paraffinembedded
tissue sections. For each section, three best-stained hotspots and the wholeslide
tumor area were evaluated using an intensity distribution score (IDS), a modified
H-score system. In addition, tumor-associated macrophages highlighted by anti-CD68
antibody were evaluated with reference to their histological locations whether in the
tumor nests or the tumor stroma. Microvessels were immunostained with anti-CD34
antibody and counted for microvessel density. Invasive ductal carcinomas variably expressed Sema4D and Plexin-Bl. Their expressions showed weak significant correlation when the whole-slide IDSs were evaluated (r=0.208, p=0.045). The average 3-hotspot IDS of Sema4D expression
showed positive association with Her-2 expression (p=0.032), while the whole-slide IDS was associated with positive hormonal receptor status (p-0.022). High average 3-
hotspot IDS of Plexin-Bl expression had higher numbers of lymph node metastasis
(p=0.032). Limiting to estrogen receptor positive cases or Her-2 overexpressed cases,
high Plexin-Bl expression by the whole-slide assessment was paradoxically associated
with absence of lymph node metastasis (p=0.009 and p=0.039, respectively). In relation
to tumor-associated macrophages, higher levels of Sema4D expression by the wholeslide
assessment were observed in lower grades of tumor stromal macrophages
(p=0.001), but no such relationship was observed for Plexin-Bl. Both Sema4D and
Plexin-Bl expressions had no relationship with the tumor nest macrophage counts. With
regard to tumor angiogenesis, Plexin-Bl expression assessed by 3-hotspot methodology
demonstrated weak positive correlation with microvessel density (r=0.206, p=0.047).
Sema4D expression was not correlated to microvessel density. Heterogeneity of Sema4D and Plexin-Bl expressions in human invasive
breast ductal carcinoma was demonstrated. Their expressions were associated with a
few traditional predictive and prognostic factors. Sema4D expressed in tumors appeared
to have an inhibitory effect on the tumor stromal macrophages. In contrast to
experimental studies, proangiogenic properties of Sema4D could not be validated. Focal
expression of Plexin-Bl might be a weak marker for a more angiogenic tumor.
However, Plexin-Bl expression was not associated with tumor-associated macrophages. |
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