Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status. Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value. Therefore, we investigated the role of these factors in ACC. Immunohistochemical analysis was performed on tissue microarrays of paraffin-embedded tissue samples from 167 ACCs, 15 adrenal adenomas and 4 normal adrenal glands. Expression was correlated with baseline parameters and clinical outcome. GLUT1 and -3 were expressed in 33 and 17% of ACC samples respectively, but in none of the benign tumours or normal adrenals glands. By contrast, TKTL1 and M2-PK were detectable in all benign tissues and the vast majority of ACCs. GLUT1 expression was strongly associated with prognosis in univariate and multivariate analysis (P!0.01), whereas GLUT3, TKTL1 and M2-PK did not correlate with clinical outcome. Patients with strong GLUT1 staining showed a considerably higher overall mortality (hazard ratio (HR) 6.34 (95% confidence interval 3.10-12.90) compared with patients with no GLUT1 staining. When analysing patients in their early stages and advanced disease separately, similar results were obtained. HR for survival was 5.31 (1.80-15.62) in patients with metatastic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2. 16-16.94). In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC.

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Background: Spindle cell tumors of the larynx are rare. In some cases, the dignity is difficult to determine. We report two cases of laryngeal spindle cell tumors.

Tumorigenesis involves energy production by aerobic glycolysis ("Warburg effect") in malignant tumors. One of the key enzymes is transketolase. Transketolase, transketolase-like-1 (TKTL1), and transketolase-like-2 are known. Antibodies against TKTL1 exist for immunohistochemical investigations. This study investigated the influence of TKTL1 on survival and metastasizing in 40 laryngeal squamous cell carcinomas (SCCs, T2-T4, 27 metastasized). Staining was assessed by an immunoreactive score (IRS) with values from 0 to 12 in primaries and their nodal metastases. The highest IRS was 8. Normal epithelium did not show an expression. Three SCCs were negative. Advanced SCCs had a higher IRS than lower stages. An IRS>4 was associated with a shorter disease specific survival, independent on the tumor stage in the multivariate analysis. Significant differences between metastasized and non-metastasized SCCs were absent, but poorly differentiated SCCs had a higher IRS in their metastases than moderate differentiated SCCs. TKTL1 overexpression is associated with a more aggressive behavior and shorter survival of laryngeal SCCs. These observations could lead to additional therapeutic options targeting a blocking of the enzyme activity.

Galectin-1, a member of the beta-galactoside-binding family, is widely expressed in epithelial and immune cells. It is involved in several normal and pathologic processes, such as cancer progression, metastasis, and immunobiology. Galectin-1 was found to be overexpressed in various cancer cells and the corresponding benign tissue. Therefore, it has been described as a marker for tumor progression in some malignancies. In the current study, the expression of galectin-1 was examined in 80 formalin-fixed, paraffin-embedded cervical tissues: 20 benign cervical specimen, 20 low-grade squamous intraepithelial lesions (LGSIL), 20 high-grade squamous intraepithelial lesions (HGSIL), and 20 invasive squamous cell carcinomas (ISCC). Immunohistochemical analyses showed that the intensity of the galectin-1 expression on stromal cells next to the transformed cells increased according to the pathologic grade: benign cervical tissue < LGSIL < HGSIL < ISCC (P < 0.001). The epithelial cells were always negative for galectin-1. These results suggest that galectin-1 expression on stromal cells increases with the histopathologic grade of cervical tissues, and it can be concluded that this increase is associated with the progression of cervical neoplasia.