ERCC1, XPF and XPA-locoregional differences and prognostic value of DNA repair protein expression in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Nucleotide excision repair protein expression has been claimed to be responsible for platinum-based chemotherapy resistance. ERCC1, XPF and XPA, core proteins in DNA repair, were evaluated regarding their prognostic value in patients with head and neck squamous cell carcinoma by looking at overall survival and time to recurrence. MATERIALS AND METHODS: Tissue microarrays were constructed from 453 cases of HNSCC, including 222 oral (49%), 126 oropharyngeal (27.8%) and 105 laryngeal (23.2%) tumours. There were 284 XPF, 293 XPA and 294 ERCC1 specimens evaluable for protein expression analysis after immunohistochemical workup. Expression levels were dichotomised into high- and low-expressing groups. Outcomes for overall survival (OS) and time to recurrence (TTR) were analysed using the Kaplan-Meier method. RESULTS: No correlation between ERCC1, XPA and XPF expression and OS was found by looking at the overall patient cohort. However, subsite analysis revealed that high ERCC1 expression was associated with a significantly inferior OS in patients with SCC of the oral cavity (p = 0.028) and showed an independent predictive value in multivariate analysis (p = 0.0123). High XPA expression showed a significantly increased OS in patients with oropharyngeal SCC (p = 0.0386). Regarding XPF, no impact on OS in any subsite could be shown. CONCLUSIONS: While high ERCC1 expression functions as a predictive marker with decreased OS in patients with squamous cell carcinoma of the oral cavity, high XPA expression shows an inverse effect in the subsite of the oropharynx, which has not been described previously. CLINICAL RELEVANCE: ERCC1 and XPA might be candidates to overcome chemotherapy resistance in subtypes of HNSCC.

[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses]. / Feinnadelaspiration (FNA) der Schilddrüse : Analyse diskrepanter zytologischer und histologischer Diagnosen.

BACKGROUND: Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. OBJECTIVES: Investigation of causes and relevance of discrepant diagnoses. MATERIALS AND METHOD: The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. RESULTS: Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. CONCLUSIONS: Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

Expression of insulin-like growth factor II mRNA-binding protein 3 in squamous cell carcinomas of the head and neck.

BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) was found overexpressed in various cancer types suggesting its possible role in carcinogenesis. Analysis of IMP3 expression in head and neck squamous cell carcinomas (HNSCC) is rare so that we evaluated it using tissue microarray method. METHOD: Immunohistochemical analysis of IMP3 was performed on samples from over 400 patients. The expression was measured semiquantitative, subsequently divided into four categories (negative, weak, medium, or strong) and correlated with several available clinicopathologic parameters. RESULTS: For HNSCC, positive IMP3 expression was observed in patients with all tumor stages (pT1-4) and nodal stages (pN0-3), showing also significant statistical correlation (P=0.023 and P=0.0013, respectively). No further correlations were found. Separate analysis according to tumor localization (oral cavity, oropharyngeal, and laryngeal) showed a significant correlation of positive IMP3 expression and overall survival (P=0.038) only in patients with tumors of the oral cavity. Multivariate analysis showed IMP3 as an independent predictive marker for oral squamous cell carcinomas (OSCC). CONCLUSION: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression might be used as an independent prognostic factor in the subgroup of OSCC.