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Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients.

Donizy P, Zietek M, Halon A, Leskiewicz M, Kozyra C, Matkowski R - Diagn Pathol (2015)

Bottom Line: It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083).Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively).Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. piotrdonizy@wp.pl.

ABSTRACT

Background: ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation.

Methods: Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry.

Results: We demonstrate that high ALCAM expression in primary melanoma cells (IRS ≥8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively).

Conclusions: High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative outcome and may indicate a more invasive phenotype of cancer cells, which would require a more intensive therapeutic strategy. Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma. Our study is the first one to evaluate the effect of increased ALCAM expression on long-term survival in melanoma patients.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemically visualized expression of ALCAM in cutaneous melanoma. Lack of ALCAM immunoreactivity in melanoma cells from primary tumor (a, 200×, hematoxylin). Cytoplasmic distribution of ALCAM in melanoma cells from primary tumor (b, IRS 6, 400×, hematoxylin). High cytoplasmic ALCAM reactivity in primary melanoma (c, IRS 12, 400×, hematoxylin). Predominantly membranous-cytoplasmic expression of ALCAM in different sizes of nests composed of malignant melanoma cells from primary tumors (d, 400×, hematoxylin). Immunohistochemical pattern of ALCAM expression in regional lymph nodes metastases. Low ALCAM immunoreactivity in metastatic melanoma cells (e, 400×, hematoxylin). High cytoplasmic reactivity of ALCAM in regional lymph node metastases (f, 200×, hematoxylin)
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Fig1: Immunohistochemically visualized expression of ALCAM in cutaneous melanoma. Lack of ALCAM immunoreactivity in melanoma cells from primary tumor (a, 200×, hematoxylin). Cytoplasmic distribution of ALCAM in melanoma cells from primary tumor (b, IRS 6, 400×, hematoxylin). High cytoplasmic ALCAM reactivity in primary melanoma (c, IRS 12, 400×, hematoxylin). Predominantly membranous-cytoplasmic expression of ALCAM in different sizes of nests composed of malignant melanoma cells from primary tumors (d, 400×, hematoxylin). Immunohistochemical pattern of ALCAM expression in regional lymph nodes metastases. Low ALCAM immunoreactivity in metastatic melanoma cells (e, 400×, hematoxylin). High cytoplasmic reactivity of ALCAM in regional lymph node metastases (f, 200×, hematoxylin)

Mentions: ALCAM expression was observed only in melanoma cells both in tissue material obtained from the primary tumor and nodal metastatic foci. No ALCAM immunoreactivity was identified in stromal compartment of tumor or lymphocytes from regional lymph nodes. Cancer cells of the primary tumor were found to exhibit two patterns of expression. Membranous-cytoplasmic localization was particularly visible in cell nests/cytoaggregates, while diffuse cytoplasmic expression without the membrane component was observed in those cancer cells which did not form evident cell nests but were a pool of scattered melanoma cells (Fig. 1 a-d). Metastatic cells displayed predominantly diffuse cytoplasmic expression (Fig. 1 e-f).Fig. 1


Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients.

Donizy P, Zietek M, Halon A, Leskiewicz M, Kozyra C, Matkowski R - Diagn Pathol (2015)

Immunohistochemically visualized expression of ALCAM in cutaneous melanoma. Lack of ALCAM immunoreactivity in melanoma cells from primary tumor (a, 200×, hematoxylin). Cytoplasmic distribution of ALCAM in melanoma cells from primary tumor (b, IRS 6, 400×, hematoxylin). High cytoplasmic ALCAM reactivity in primary melanoma (c, IRS 12, 400×, hematoxylin). Predominantly membranous-cytoplasmic expression of ALCAM in different sizes of nests composed of malignant melanoma cells from primary tumors (d, 400×, hematoxylin). Immunohistochemical pattern of ALCAM expression in regional lymph nodes metastases. Low ALCAM immunoreactivity in metastatic melanoma cells (e, 400×, hematoxylin). High cytoplasmic reactivity of ALCAM in regional lymph node metastases (f, 200×, hematoxylin)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489046&req=5

Fig1: Immunohistochemically visualized expression of ALCAM in cutaneous melanoma. Lack of ALCAM immunoreactivity in melanoma cells from primary tumor (a, 200×, hematoxylin). Cytoplasmic distribution of ALCAM in melanoma cells from primary tumor (b, IRS 6, 400×, hematoxylin). High cytoplasmic ALCAM reactivity in primary melanoma (c, IRS 12, 400×, hematoxylin). Predominantly membranous-cytoplasmic expression of ALCAM in different sizes of nests composed of malignant melanoma cells from primary tumors (d, 400×, hematoxylin). Immunohistochemical pattern of ALCAM expression in regional lymph nodes metastases. Low ALCAM immunoreactivity in metastatic melanoma cells (e, 400×, hematoxylin). High cytoplasmic reactivity of ALCAM in regional lymph node metastases (f, 200×, hematoxylin)
Mentions: ALCAM expression was observed only in melanoma cells both in tissue material obtained from the primary tumor and nodal metastatic foci. No ALCAM immunoreactivity was identified in stromal compartment of tumor or lymphocytes from regional lymph nodes. Cancer cells of the primary tumor were found to exhibit two patterns of expression. Membranous-cytoplasmic localization was particularly visible in cell nests/cytoaggregates, while diffuse cytoplasmic expression without the membrane component was observed in those cancer cells which did not form evident cell nests but were a pool of scattered melanoma cells (Fig. 1 a-d). Metastatic cells displayed predominantly diffuse cytoplasmic expression (Fig. 1 e-f).Fig. 1

Bottom Line: It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083).Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively).Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. piotrdonizy@wp.pl.

ABSTRACT

Background: ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation.

Methods: Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry.

Results: We demonstrate that high ALCAM expression in primary melanoma cells (IRS ≥8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively).

Conclusions: High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative outcome and may indicate a more invasive phenotype of cancer cells, which would require a more intensive therapeutic strategy. Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma. Our study is the first one to evaluate the effect of increased ALCAM expression on long-term survival in melanoma patients.

No MeSH data available.


Related in: MedlinePlus