Prognostic Value of Malic Enzyme and ATP-Citrate Lyase in Non-Small Cell Lung Cancer of the Young and the Elderly

<div><p>Background</p><p>Lung cancer is the leading cause of death among malignancies worldwide. Understanding its biology is therefore of pivotal importance to improve patient’s prognosis. In contrast to non-neoplastic tissues, cancer cells utilize glucose mainly for production of basic cellular modules ‘(i.e. nucleotides, aminoacids, fatty acids). In cancer, Malic enzyme (ME) and ATP-citrate lyase (ACLY) are key enzymes linking aerobic glycolysis and fatty acid synthesis and may therefore be of biological and prognostic significance in non-small cell lung cancer (NSCLC).</p><p>Material and Methods</p><p>ME and ACLY expression was analyzed in 258 NSCLC in correlation with clinico-pathological parameters including patient’s survival.</p><p>Results</p><p>Though, overall expression of both enzymes correlated positively, ACLY was associated with local tumor stage, whereas ME correlated with occurrence of mediastinal lymph node metastases. Young patients overexpressing ACLY and/or ME had a significantly longer overall survival. This proved to be an independent prognostic factor. This contrasts older NSCLC patients, in whom overexpression of ACLY and/or ME appears to predict the opposite.</p><p>Conclusion</p><p>In NSCLC, ME and ACLY show different enzyme expressions relating to local and mediastinal spread. Most important, we detected an inverse prognostic impact of ACLY and/or ME overexpression in young and elderly patients. It can therefore be expected, that treatment of NSCLC especially, if targeting metabolic pathways, requires different strategies in different age groups.</p></div

Immunohistological expression of ACLY (A – D) and ME (E – H).

<p>(A)–(D) Specific ACLY-expression was detectable in the nucleus, or in the cytoplasm. (A); tumor tissue without specific ACLY staining—intensity score = 0; (B) weak specific cytoplasmic ACLY staining—intensity score = 1; (C) moderate nuclear ACLY staining—intensity score = 2 and moderate cytoplasmic ACLY staining—intensity score = 2; (D) strong cytoplasmic ACLY staining—intensity score = 3, additionally moderate nuclear staining is present; (E)–(H) Specific cytoplasmic expression of ME, (E) tumor tissue without specific cytoplasmic ME staining—intensity score = 0 (F); weak specific cytoplasmic ME staining—intensity score = 1 (G); moderate cytoplasmic ME staining—intensity score = 2 (H) and with strong specific cytoplasmic ME staining—intensity score = 3 (E). (Magnification; 20x)</p

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011

Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.

Additional file 3: Table S2. of Tumour stage distribution and survival of malignant melanoma in Germany 2002–2011

Malignant melanoma patients aged 35 years and above by age at diagnosis, sex, UICC stage, year of diagnosis, place of residence and ‘diagnosis during screening’, N = 34 739 (UICC 0 and X excluded) (DOCX 40 kb

Additional file 4: Table S3. of Tumour stage distribution and survival of malignant melanoma in Germany 2002–2011

Relative 5-year survival of malignant melanoma patients diagnosed between 2002 and 2011, overall (UICC 0-IV, X) (N = 60 672) and for patients with invasive tumours (UICC I – IV, X) stratified by age, sex, UICC stage, ‘diagnosis during screening’ and place of residence (N = 49 351) (DOCX 39 kb