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Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: prominent expression of P-cadherin.

Ben Hamida A, Labidi IS, Mrad K, Charafe-Jauffret E, Ben Arab S, Esterni B, Xerri L, Viens P, Bertucci F, Birnbaum D, Jacquemier J - BMC Cancer (2008)

Bottom Line: In Tunisia, IBC is associated with a high death rate.We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001).P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche en Cancérologie de Marseille, Département d'Oncologie Moléculaire, UMR599 Inserm, Marseille, France. azza.benhamida@gmail.com

ABSTRACT

Background: Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC.

Methods: To determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays.

Results: We considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001). The most differentially-expressed protein between IBCs and non-IBCs was P-cadherin. P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases. Logistic regression determined that the most discriminating markers between IBCs and non-IBCs were P-cadherin (OR = 4.9, p = 0.0019) MIB1 (OR = 3.6, p = 0.001), CK14 (OR = 2.7, p = 0.02), and ERBB2 (OR = 2.3, p = 0.06).

Conclusion: Tunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation.

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Immunohistochemistry on tissue microarray sections of breast cancers of the luminal subtype. A: Expression of estrogen receptor in 100% of tumor cells in a grade III inflammatory case. B: Strong expression of P-cadherin in 100% of tumor cells in the same case. C: Higher magnification showing the cell membrane localization. D: Expression of estrogen receptor in 100 % of tumor cells in a more differentiated (grade II) inflammatory case. E: Moderate expression of P- cadherin in 100% of tumor cells in the same case. F: Higher magnification showing the cell membrane localization. G: Luminal grade II non inflammatory case with 100% estrogen receptor-positive cells. H: Absence of expression of P-cadherin in the same non inflammatory case; note the positive internal control on myoepithelial cells of the normal duct. I: Higher magnification showing the cell membrane localization of the myoepithelial cells by contrast to the negativity of the luminal normal cells.
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Figure 1: Immunohistochemistry on tissue microarray sections of breast cancers of the luminal subtype. A: Expression of estrogen receptor in 100% of tumor cells in a grade III inflammatory case. B: Strong expression of P-cadherin in 100% of tumor cells in the same case. C: Higher magnification showing the cell membrane localization. D: Expression of estrogen receptor in 100 % of tumor cells in a more differentiated (grade II) inflammatory case. E: Moderate expression of P- cadherin in 100% of tumor cells in the same case. F: Higher magnification showing the cell membrane localization. G: Luminal grade II non inflammatory case with 100% estrogen receptor-positive cells. H: Absence of expression of P-cadherin in the same non inflammatory case; note the positive internal control on myoepithelial cells of the normal duct. I: Higher magnification showing the cell membrane localization of the myoepithelial cells by contrast to the negativity of the luminal normal cells.

Mentions: IHC was done on IBCs and non-IBCs using three TMA slides for each marker. We compared the expression of the markers only for the infiltrating ductal cases, i.e. 86 IBC cases and 386 non-IBC cases. We observed differences between the two series for: ER negativity (53.85% IBCs, 26.26 % non-IBCs; p < 0.001), PR negativity (52.86% IBCs, 35.39% non-IBCs; p < 0.01), ERBB2 positivity (33.33% IBCs, 14.49% non-IBCs; p < 0.001), CK14 positivity (19.15% IBCs, 5.45% non-IBCs; p < 0.01), P-cadherin positivity (75.93% IBCs, 48.16% non-IBCs; p < 0.001) (Figure 1) and proliferative rate expressed by a Ki67 index (MIB1) higher than 20% (41.1% IBCs, 12.98% non-IBCs; p < 0.001) (Table 3).


Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: prominent expression of P-cadherin.

Ben Hamida A, Labidi IS, Mrad K, Charafe-Jauffret E, Ben Arab S, Esterni B, Xerri L, Viens P, Bertucci F, Birnbaum D, Jacquemier J - BMC Cancer (2008)

Immunohistochemistry on tissue microarray sections of breast cancers of the luminal subtype. A: Expression of estrogen receptor in 100% of tumor cells in a grade III inflammatory case. B: Strong expression of P-cadherin in 100% of tumor cells in the same case. C: Higher magnification showing the cell membrane localization. D: Expression of estrogen receptor in 100 % of tumor cells in a more differentiated (grade II) inflammatory case. E: Moderate expression of P- cadherin in 100% of tumor cells in the same case. F: Higher magnification showing the cell membrane localization. G: Luminal grade II non inflammatory case with 100% estrogen receptor-positive cells. H: Absence of expression of P-cadherin in the same non inflammatory case; note the positive internal control on myoepithelial cells of the normal duct. I: Higher magnification showing the cell membrane localization of the myoepithelial cells by contrast to the negativity of the luminal normal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2267802&req=5

Figure 1: Immunohistochemistry on tissue microarray sections of breast cancers of the luminal subtype. A: Expression of estrogen receptor in 100% of tumor cells in a grade III inflammatory case. B: Strong expression of P-cadherin in 100% of tumor cells in the same case. C: Higher magnification showing the cell membrane localization. D: Expression of estrogen receptor in 100 % of tumor cells in a more differentiated (grade II) inflammatory case. E: Moderate expression of P- cadherin in 100% of tumor cells in the same case. F: Higher magnification showing the cell membrane localization. G: Luminal grade II non inflammatory case with 100% estrogen receptor-positive cells. H: Absence of expression of P-cadherin in the same non inflammatory case; note the positive internal control on myoepithelial cells of the normal duct. I: Higher magnification showing the cell membrane localization of the myoepithelial cells by contrast to the negativity of the luminal normal cells.
Mentions: IHC was done on IBCs and non-IBCs using three TMA slides for each marker. We compared the expression of the markers only for the infiltrating ductal cases, i.e. 86 IBC cases and 386 non-IBC cases. We observed differences between the two series for: ER negativity (53.85% IBCs, 26.26 % non-IBCs; p < 0.001), PR negativity (52.86% IBCs, 35.39% non-IBCs; p < 0.01), ERBB2 positivity (33.33% IBCs, 14.49% non-IBCs; p < 0.001), CK14 positivity (19.15% IBCs, 5.45% non-IBCs; p < 0.01), P-cadherin positivity (75.93% IBCs, 48.16% non-IBCs; p < 0.001) (Figure 1) and proliferative rate expressed by a Ki67 index (MIB1) higher than 20% (41.1% IBCs, 12.98% non-IBCs; p < 0.001) (Table 3).

Bottom Line: In Tunisia, IBC is associated with a high death rate.We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001).P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche en Cancérologie de Marseille, Département d'Oncologie Moléculaire, UMR599 Inserm, Marseille, France. azza.benhamida@gmail.com

ABSTRACT

Background: Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC.

Methods: To determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays.

Results: We considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001). The most differentially-expressed protein between IBCs and non-IBCs was P-cadherin. P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases. Logistic regression determined that the most discriminating markers between IBCs and non-IBCs were P-cadherin (OR = 4.9, p = 0.0019) MIB1 (OR = 3.6, p = 0.001), CK14 (OR = 2.7, p = 0.02), and ERBB2 (OR = 2.3, p = 0.06).

Conclusion: Tunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation.

Show MeSH
Related in: MedlinePlus