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. 2010 Apr 12:5:22.
doi: 10.1186/1746-1596-5-22.

Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1

Gian Kayser  1 , Ahmad Kassem, Wulf Sienel, Luzie Schulte-Uentrop, Dominik Mattern, Konrad Aumann, Elmar Stickeler, Martin Werner, Bernward Passlick, Axel zur Hausen
Affiliations

Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1

Gian Kayser et al. Diagn Pathol. .

Abstract

Aims: As one of the five lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. LDH5 overexpression in cancer cells induces an upregulated glycolytic metabolism and reduced dependence on the presence of oxygen. Here we analyzed LDH5 protein expression in a well characterized large cohort of primary lung cancers in correlation to clinico-pathological data and its possible impact on patient survival.

Methods: Primary lung cancers (n = 269) and non neoplastic lung tissue (n = 35) were tested for LDH5 expression by immunohistochemistry using a polyclonal LDH5 antibody (ab53010). The results of LDH5 expression were correlated to clinico-pathological data as well as to patient's survival. In addition, the results of the previously tested transketolase like 1 protein (TKTL1) expression were correlated to LDH5 expression.

Results: 89.5% (n = 238) of NSCLC revealed LDH5 expression whereas LDH5 expression was not detected in non neoplastic lung tissues (n = 34) (p < 0.0001). LDH5 overexpression was associated with histological type (adenocarcinoma = 57%, squamous cell carcinoma = 45%, large cell carcinoma = 46%, p = 0.006). No significant correlation could be detected with regard to TNM-stage, grading or survival. A two sided correlation between the expression of TKTL1 and LDH5 could be shown (p = 0.002) within the overall cohort as well as for each grading and pN group. A significant correlation between LDH5 and TKTL1 within each histologic tumortype could not be revealed.

Conclusions: LDH5 is overexpressed in NSCLC and could hence serve as an additional marker for malignancy. Furthermore, LDH5 correlates positively with the prognostic marker TKTL1. Our results confirm a close link between the two metabolic enzymes and indicate an alteration in the glucose metabolism in the process of malignant transformation.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of LDH5 in NSCLC. Upper left: Squamous cell carcinoma without immunohistochemically detectable expression of LDH5; Upper right: Adenocarcinoma with weak expression of LDH5 - score 1; lower left: Adenocarcinoma with moderate expression of LDH5 - score 2; lower right: Adenocarcinoma with strong expression of LDH5 - score 3. (200×)
Figure 2
Figure 2
Kaplan-Meier survival curve for the separate pT-stages (p < 0.001).
Figure 3
Figure 3
Kaplan-Meier survival curve for the separate pN-stages (p < 0.001).
Figure 4
Figure 4
Kaplan-Meier survival curve for the separate UICC-stages (p < 0.001).
Figure 5
Figure 5
Kaplan-Meier survival curve in regard to histologic type (p = 0.123).
Figure 6
Figure 6
Kaplan-Meier survival curve comparing smokers vs non-smokers (p = 0.087).
Figure 7
Figure 7
Kaplan-Meier survival curve for LDH5-positive vs LDH5-negative tumors (p = 0.165).
Figure 8
Figure 8
Kaplan-Meier survival curve comparing overexpression of LDH5 in smokers (a) (p = 0.16) and non.smokers (b) (p = 0.098).
Figure 9
Figure 9
Kaplan-Meier survival curves comparing LDH5 expression according to Koukourakis et al [13]in all NSCLC (p = 0.785) (a), AC combined with SCC (p = 0.551) (b), AC (p = 0.662) (c) and SCC (p = 0.145) (d).
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