Estrogen and Progesterone hormone receptor expression in oral cavity cancer.

BACKGROUND: Recent studies have shown an increase in the incidence of oral squamous cell carcinoma (OSCC) in younger patients. The hypothesis that tumors could be hormonally induced during pregnancy or in young female patients without the well-known risk factors alcohol or tobacco abuse seems to be plausible. MATERIAL AND METHODS: Estrogen Receptor alpha (ERα) and Progesterone Receptor (PR) expression were analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen. OSCCs were stratified in a young female (n=7) study cohort and older patients (n=46). In the young female study cohort three patients (n=3/7) developed OSCC during or shortly after pregnancy. Breast cancer tissues were used as positive control for ERα and PR expression. RESULTS: ERα expression was found in four oral precursor lesions (squamous intraepithelial neoplasia, SIN I-III, n=4/35, 11%) and in five OSCC specimen (n=5/46, 11%). The five ERα positive OSCC samples were older male patients. All patients within the young female study cohort were negatively stained for both ERα and PR. CONCLUSIONS: ER expression could be regarded as a seldom risk factor for OSCC. PR expression seems to be not relevant for the development of OSCC.

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

Purpose. Thiamine-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the pentose phosphate pathway transketolases (TKTs), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate dehydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are crucial factors for tumor metabolism. The expression of these enzymes has not been analyzed for carcinogenesis of oral squamous cell carcinoma (OSCC) with special focus on new targeted metabolic therapies as yet. Methods. TDEs PDH, KGDH (OGDH), and BCKDH were analyzed in normal oral mucosa (n = 14), oral precursor lesions (simple hyperplasia, n = 21; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 46) by immunohistochemistry and western blot (WB) analysis in OSCC tumor cell lines. Results. Although the total numbers of PDH and KGDH (OGDH) positive samples decreased in OSCC, both enzymes were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue. BCKDH has been demonstrated to be significantly overexpressed in the carcinogenesis of OSCC. Specificity of the antibodies was confirmed by WB analysis. Conclusions. This is the first study showing increased expression of TDEs in OSCC. Metabolic targeting of TDEs (including TKTs) by antagonistic compounds like oxythiamine or oxybenfothiamine may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies (AU)

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Monitoring a 'metabolic shift' after surgical resection of oral squamous cell carcinomas by serum lactate dehydrogenase.

OBJECTIVES: Monitoring surgical removal of oral squamous cell carcinomas (OSCC) is being routinely performed through clinical and imaging follow-up. We analyzed the potential use of serum lactate, lactate dehydrogenase (LDH), and LDH isoenzymes (LDH 1-5) as biomarkers in blood for the monitoring of surgical removal of OSCC. MATERIALS AND METHODS: Serum lactate, LDH, and LDH isoenzymes (LDH 1-5) have been prospectively assessed in healthy individuals (n = 19), patients with OSCC (n = 34: primary OSCC, n = 32 and recurrent OSCC, n = 2) before surgery and after curative tumor resection (n = 26). LDHA and LDHB expressions were analyzed by immunohistochemistry (IHC) in the same OSCC tumor specimen. RESULTS: Positive LDHA tumor tissue expression measured by IHC (n = 34/34, 100%) was significantly associated with increased serum LDH-5 (n = 24/34, 71%, P = 0.0258) but weak significantly associated with increased total serum LDH (n = 23/34, 68%, P = 0.0592). Positive LDHB tumor tissue expression measured by IHC (n = 25/34, 74%) was significantly associated with increased total serum LDH (P = 0.0172). After surgery, serum LDH and LDH-5 isoenzyme significantly decreased and LDH-1 significantly increased in the aftercare. A significantly inverse correlation of LDHA with LDHB IHC scores was found (P < 0.0001). CONCLUSIONS: The association of LDHA and LDHB measured by IHC with serum LDH indicates that analyzing this enzyme could serve as a favorable 'liquid biopsy' (non-invasive diagnostic tool) for OSCC.

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

PURPOSE: Thiamine-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the pentose phosphate pathway transketolases (TKTs), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate dehydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are crucial factors for tumor metabolism. The expression of these enzymes has not been analyzed for carcinogenesis of oral squamous cell carcinoma (OSCC) with special focus on new targeted metabolic therapies as yet. METHODS: TDEs PDH, KGDH (OGDH), and BCKDH were analyzed in normal oral mucosa (n = 14), oral precursor lesions (simple hyperplasia, n = 21; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 46) by immunohistochemistry and western blot (WB) analysis in OSCC tumor cell lines. RESULTS: Although the total numbers of PDH and KGDH (OGDH) positive samples decreased in OSCC, both enzymes were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue. BCKDH has been demonstrated to be significantly overexpressed in the carcinogenesis of OSCC. Specificity of the antibodies was confirmed by WB analysis. CONCLUSIONS: This is the first study showing increased expression of TDEs in OSCC. Metabolic targeting of TDEs (including TKTs) by antagonistic compounds like oxythiamine or oxybenfothiamine may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

23-Year-Old Female with an Inflammatory Myofibroblastic Tumour of the Breast: A Case Report and a Review of the Literature.

Purpose: Inflammatory myofibroblastic tumours (IMT) are a subcategory of inflammatory pseudotumours (IPT). They arise most commonly in the abdominopelvic region, lung and retroperitoneum, but virtually any anatomical site may be involved. Predominantly children and adolescents are affected and there is a tendency for local recurrence. In the literature up to the present, 20 patients have been reported with an IPT/IMT of the breast. We would like to present another patient with this unusual tumour entity of the breast and discuss the literature. Patient and Examinations: A 23-year-old woman presented with a painless lump in her left breast. There was no history of breast cancer in her family. Sonography showed a hypoechoic heterogeneous solid mass with irregular margins. A core needle biopsy revealed a tumour of high cellularity and a densely collagenous background. Immunohistochemically, the spindle-shaped cells were immunoreactive to smooth muscle actin and ALK-1 protein. Additional FISH analysis proved ALK rearrangements on chromosome 2p23 leading to the diagnosis of an IMT. Wide surgical excision was performed with no evidence of local recurrence after 12 months. Conclusion: Three of the above mentioned 20 patients with IMT/IPT of the breast developed a recurrent tumour, none presented with distant metastasis. A significant recurrence rate of 15 % leads to a clinically and sonographically close follow-up in these patients.