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Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery.

Planeix F, Siraj MA, Bidard FC, Robin B, Pichon C, Sastre-Garau X, Antoine M, Ghinea N - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors.The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups.FSHR+ vessels did not express VEGFR2.

View Article: PubMed Central - PubMed

Affiliation: INSERM "Tumoral Angiogenesis" Laboratory, Curie Institute, Research Center, Translational Research Department, 26 rue d'Ulm, Paris, France. francois.planeix@curie.fr.

ABSTRACT

Background: Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.

Methods: We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.

Results: The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm(2), respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels' density (p < 0.001) and tumor size (p = 0.01).

Conclusion: Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.

No MeSH data available.


Related in: MedlinePlus

FSHR expression in blood vessels associated with strands of invasive breast cancer cells. A) Image of invasive strands of breast cancer cells (asterisk) at low magnification. B) Detail of an invasive strand of cancer cells located at 4 mm outside the tumor border (dashed line in A). Immunohistochemical analysis was performed as described in the legend of Figure 2. Scale bars: 500 μm (A) and 100 μm (B).
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Fig3: FSHR expression in blood vessels associated with strands of invasive breast cancer cells. A) Image of invasive strands of breast cancer cells (asterisk) at low magnification. B) Detail of an invasive strand of cancer cells located at 4 mm outside the tumor border (dashed line in A). Immunohistochemical analysis was performed as described in the legend of Figure 2. Scale bars: 500 μm (A) and 100 μm (B).

Mentions: The blood vessels that expressed FSHR were located in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. FSHR+ blood vessels within these tumor zones (Figure 2) were similar in caliber and structural components to FSHR-negative breast vessels associated with the normal-appearing tissue located at a distance greater than 10 mm outside the tumors. Blood vessels associated with invasive tumor cell strands expressed also the endothelial FSHR (Figure 3). The total number of FSHR+ blood vessel we counted was 4,987. Approximately 62% of blood vessels expressing FSHR were capillaries (diameter ≤ 10 μm) and 25% were venules (10 μm < diameter ≤ 100 μm). Robust staining for FSHR was also found on small arterioles of ~ 25 μm in diameter (12%). Faint staining for FSHR was noticed on venules (100 μm < diameter ≤ 300 μm; 0.6%). All four molecular subtypes of breast cancer expressed almost similar densities of FSHR stained blood vessels (Table 1). Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm2, respectively).Figure 2


Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery.

Planeix F, Siraj MA, Bidard FC, Robin B, Pichon C, Sastre-Garau X, Antoine M, Ghinea N - J. Exp. Clin. Cancer Res. (2015)

FSHR expression in blood vessels associated with strands of invasive breast cancer cells. A) Image of invasive strands of breast cancer cells (asterisk) at low magnification. B) Detail of an invasive strand of cancer cells located at 4 mm outside the tumor border (dashed line in A). Immunohistochemical analysis was performed as described in the legend of Figure 2. Scale bars: 500 μm (A) and 100 μm (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4321709&req=5

Fig3: FSHR expression in blood vessels associated with strands of invasive breast cancer cells. A) Image of invasive strands of breast cancer cells (asterisk) at low magnification. B) Detail of an invasive strand of cancer cells located at 4 mm outside the tumor border (dashed line in A). Immunohistochemical analysis was performed as described in the legend of Figure 2. Scale bars: 500 μm (A) and 100 μm (B).
Mentions: The blood vessels that expressed FSHR were located in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. FSHR+ blood vessels within these tumor zones (Figure 2) were similar in caliber and structural components to FSHR-negative breast vessels associated with the normal-appearing tissue located at a distance greater than 10 mm outside the tumors. Blood vessels associated with invasive tumor cell strands expressed also the endothelial FSHR (Figure 3). The total number of FSHR+ blood vessel we counted was 4,987. Approximately 62% of blood vessels expressing FSHR were capillaries (diameter ≤ 10 μm) and 25% were venules (10 μm < diameter ≤ 100 μm). Robust staining for FSHR was also found on small arterioles of ~ 25 μm in diameter (12%). Faint staining for FSHR was noticed on venules (100 μm < diameter ≤ 300 μm; 0.6%). All four molecular subtypes of breast cancer expressed almost similar densities of FSHR stained blood vessels (Table 1). Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm2, respectively).Figure 2

Bottom Line: These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors.The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups.FSHR+ vessels did not express VEGFR2.

View Article: PubMed Central - PubMed

Affiliation: INSERM "Tumoral Angiogenesis" Laboratory, Curie Institute, Research Center, Translational Research Department, 26 rue d'Ulm, Paris, France. francois.planeix@curie.fr.

ABSTRACT

Background: Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.

Methods: We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.

Results: The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm(2), respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels' density (p < 0.001) and tumor size (p = 0.01).

Conclusion: Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.

No MeSH data available.


Related in: MedlinePlus