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Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma.

Liu JL, Chen FF, Lung J, Lo CH, Lee FH, Lu YC, Hung CH - Br. J. Cancer (2014)

Bottom Line: High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm.Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis.Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pathology, St. Martin De Porres Hospital, No. 565, Sector 2, Daya Road, Chiayi City 600, Taiwan [2] Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Township, Taoyuan County 333, Taiwan.

ABSTRACT

Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs.

Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated.

Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.

Conclusions: We suggested that autophagy was altered during cancer initiation and progression. Autophagy impairment contributed to cancer progression in advanced OSCCs.

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Related in: MedlinePlus

The results of in situ hybridisation for p62 mRNA in normal oral mucosas, verrucous hyperplasias, and OSCCs.(A) Representative cases of p62 mRNA in situ hybridization (original magnification × 400). Most cases show limited to undetectable level of p62 mRNA. Some cases exhibit prominent p62 mRNA expression. (B) The difference of p62 mRNA expression in normal oral mucosas, verrucous hyperplasias, and OSCCs. It is not statistically significant (P=0.103). (C) The relationship of p62 mRNA and protein expressions. High expression of mRNA is associated with high expression of protein in the cytoplasm.
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fig3: The results of in situ hybridisation for p62 mRNA in normal oral mucosas, verrucous hyperplasias, and OSCCs.(A) Representative cases of p62 mRNA in situ hybridization (original magnification × 400). Most cases show limited to undetectable level of p62 mRNA. Some cases exhibit prominent p62 mRNA expression. (B) The difference of p62 mRNA expression in normal oral mucosas, verrucous hyperplasias, and OSCCs. It is not statistically significant (P=0.103). (C) The relationship of p62 mRNA and protein expressions. High expression of mRNA is associated with high expression of protein in the cytoplasm.

Mentions: The p62 mRNA expression detected using RNAscope showed no significant difference between normal oral mucosas, verrucous hyperplasias, and OSCCs (P=0.103; Figure 3A and B). Most of the cases (240 out of 279, 86.02%) exhibited low p62 gene expression. In addition, high expression of p62 mRNA was associated with high expression of p62 protein in the cytoplasm (P=0.004; Figure 3C).


Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma.

Liu JL, Chen FF, Lung J, Lo CH, Lee FH, Lu YC, Hung CH - Br. J. Cancer (2014)

The results of in situ hybridisation for p62 mRNA in normal oral mucosas, verrucous hyperplasias, and OSCCs.(A) Representative cases of p62 mRNA in situ hybridization (original magnification × 400). Most cases show limited to undetectable level of p62 mRNA. Some cases exhibit prominent p62 mRNA expression. (B) The difference of p62 mRNA expression in normal oral mucosas, verrucous hyperplasias, and OSCCs. It is not statistically significant (P=0.103). (C) The relationship of p62 mRNA and protein expressions. High expression of mRNA is associated with high expression of protein in the cytoplasm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150268&req=5

fig3: The results of in situ hybridisation for p62 mRNA in normal oral mucosas, verrucous hyperplasias, and OSCCs.(A) Representative cases of p62 mRNA in situ hybridization (original magnification × 400). Most cases show limited to undetectable level of p62 mRNA. Some cases exhibit prominent p62 mRNA expression. (B) The difference of p62 mRNA expression in normal oral mucosas, verrucous hyperplasias, and OSCCs. It is not statistically significant (P=0.103). (C) The relationship of p62 mRNA and protein expressions. High expression of mRNA is associated with high expression of protein in the cytoplasm.
Mentions: The p62 mRNA expression detected using RNAscope showed no significant difference between normal oral mucosas, verrucous hyperplasias, and OSCCs (P=0.103; Figure 3A and B). Most of the cases (240 out of 279, 86.02%) exhibited low p62 gene expression. In addition, high expression of p62 mRNA was associated with high expression of p62 protein in the cytoplasm (P=0.004; Figure 3C).

Bottom Line: High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm.Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis.Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pathology, St. Martin De Porres Hospital, No. 565, Sector 2, Daya Road, Chiayi City 600, Taiwan [2] Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Township, Taoyuan County 333, Taiwan.

ABSTRACT

Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs.

Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated.

Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs.

Conclusions: We suggested that autophagy was altered during cancer initiation and progression. Autophagy impairment contributed to cancer progression in advanced OSCCs.

Show MeSH
Related in: MedlinePlus