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Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers.

Al-Attar A, Gossage L, Fareed KR, Shehata M, Mohammed M, Zaitoun AM, Soomro I, Lobo DN, Abbotts R, Chan S, Madhusudan S - Br. J. Cancer (2010)

Bottom Line: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05).Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068).A trend was noticed with advanced stage (P=0.077).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, UK.

ABSTRACT

Background: Altered DNA repair may be associated with aggressive tumour biology and impact upon response to chemotherapy and radiotherapy. We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, gastro-oesophageal, and pancreatico-biliary cancer.

Methods: Formalin-fixed human ovarian, gastro-oesophageal, and pancreatico-biliary cancers were constructed into TMAs. Expression of APE1 was analysed by IHC and correlated to clinicopathological variables.

Results: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05). In gastro-oesophageal cancers previously exposed to neoadjuvant chemotherapy, 34.8% (16 out of 46) of tumours were positive in the nucleus and this correlated with shorter overall survival (P=0.005), whereas cytoplasmic localisation correlated with tumour dedifferentiation (P=0.034). In pancreatico-biliary cancer, nuclear staining was seen in 44% (32 out of 72) of tumours. Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068). A trend was noticed with advanced stage (P=0.077).

Conclusions: Positive clinicopathological correlations of APE1 expression suggest that APE1 is a potential drug target in ovarian, gastro-oesophageal, and pancreatico-biliary cancers.

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Microphotographs of ovarian cancer (A), gastric cancer (B), and PAC (C) showing positive nuclear APE1 expression (magnification × 200).
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fig1: Microphotographs of ovarian cancer (A), gastric cancer (B), and PAC (C) showing positive nuclear APE1 expression (magnification × 200).

Mentions: Apyrimidinic endonuclease-1 expression was noted both in the cytoplasmic and nuclear compartments in ovarian cancer; however, nuclear staining was more prevalent (Table 2). Of the 135 evaluable cores, 97 had nuclear expression (71.9%), but only 40 had cytoplasmic expression (29.6%). It was seen more often localised to the nucleus only (45.9%) (Figure 1A) as compared with 3.7% showing exclusively cytoplasmic staining. There was a significant difference in the level of APE1 expression among the different histological subtypes of ovarian cancer, with serous and mucinous tumours displaying nuclear APE1 more frequently than endometrioid and clear-cell carcinomas (P=0.006) (Table 3). Nuclear localisation of APE1 correlated with a lower likelihood of achieving optimal debulking after initial surgery (P=0.009), suggesting a more aggressive phenotype. This was also reflected on survival; APE1-positive cases had worse overall survival (median survival time=52 months) as compared with 71 months for APE1-negative patients. This difference was statistically significant as shown in the Kaplan–Meier graph and log-rank test (P=0.05) (Figure 2A). No significant correlations were seen between APE1 and FIGO stage or with histological grade.


Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers.

Al-Attar A, Gossage L, Fareed KR, Shehata M, Mohammed M, Zaitoun AM, Soomro I, Lobo DN, Abbotts R, Chan S, Madhusudan S - Br. J. Cancer (2010)

Microphotographs of ovarian cancer (A), gastric cancer (B), and PAC (C) showing positive nuclear APE1 expression (magnification × 200).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837561&req=5

fig1: Microphotographs of ovarian cancer (A), gastric cancer (B), and PAC (C) showing positive nuclear APE1 expression (magnification × 200).
Mentions: Apyrimidinic endonuclease-1 expression was noted both in the cytoplasmic and nuclear compartments in ovarian cancer; however, nuclear staining was more prevalent (Table 2). Of the 135 evaluable cores, 97 had nuclear expression (71.9%), but only 40 had cytoplasmic expression (29.6%). It was seen more often localised to the nucleus only (45.9%) (Figure 1A) as compared with 3.7% showing exclusively cytoplasmic staining. There was a significant difference in the level of APE1 expression among the different histological subtypes of ovarian cancer, with serous and mucinous tumours displaying nuclear APE1 more frequently than endometrioid and clear-cell carcinomas (P=0.006) (Table 3). Nuclear localisation of APE1 correlated with a lower likelihood of achieving optimal debulking after initial surgery (P=0.009), suggesting a more aggressive phenotype. This was also reflected on survival; APE1-positive cases had worse overall survival (median survival time=52 months) as compared with 71 months for APE1-negative patients. This difference was statistically significant as shown in the Kaplan–Meier graph and log-rank test (P=0.05) (Figure 2A). No significant correlations were seen between APE1 and FIGO stage or with histological grade.

Bottom Line: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05).Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068).A trend was noticed with advanced stage (P=0.077).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, UK.

ABSTRACT

Background: Altered DNA repair may be associated with aggressive tumour biology and impact upon response to chemotherapy and radiotherapy. We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, gastro-oesophageal, and pancreatico-biliary cancer.

Methods: Formalin-fixed human ovarian, gastro-oesophageal, and pancreatico-biliary cancers were constructed into TMAs. Expression of APE1 was analysed by IHC and correlated to clinicopathological variables.

Results: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05). In gastro-oesophageal cancers previously exposed to neoadjuvant chemotherapy, 34.8% (16 out of 46) of tumours were positive in the nucleus and this correlated with shorter overall survival (P=0.005), whereas cytoplasmic localisation correlated with tumour dedifferentiation (P=0.034). In pancreatico-biliary cancer, nuclear staining was seen in 44% (32 out of 72) of tumours. Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068). A trend was noticed with advanced stage (P=0.077).

Conclusions: Positive clinicopathological correlations of APE1 expression suggest that APE1 is a potential drug target in ovarian, gastro-oesophageal, and pancreatico-biliary cancers.

Show MeSH
Related in: MedlinePlus