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Background The pathogenesis of radiation-induced sarcomas (RISs) is not well known. In RIS, TP53 mutations are frequent, but little is known about Mdm2-p53 interaction, which is a recent therapeutic target of sarcomas. Methods We studied the immunohistochemical expression of Mdm2 and p53 of 8 RISs. The intervals between radiation therapy and diagnosis of secondary sarcomas ranged from 3 to 17 years. Results Mdm2 expression was more common in de novo sarcomas than RISs (75% vs 37.5%), and p53 expression was more common in RISs than in de novo cases (75% vs 37.5%). While half of the RISs were Mdm2(–)/p53(+), none of de novo cases showed such combination; while half of de novo sarcomas were Mdm2(+)/p53(–), which are a candidate group of Mdm2 inhibitors, only 1 RIS showed such a combination. Variable immunoprofiles observed in both groups did not correlate with tumor types, except that all of 2 myxofibrosarcomas were Mdm2(+)/p53(+). Conclusions In conclusion, we speculated that both radiation-induced and de novo sarcomagenesis are not due to a unique genetic mechanism. Mdm2-expression without p53 overexpression in 1 case of RIS decreases the future possibility of applying Mdm2 inhibitors on a subset of these difficult tumors.

The oral cavity and oropharynx are very unusual sites of systemic metastases from primary cancers of other organs, which account for only about 1-2% of oral malignant tumors.1,2 A tendancy not to consider this rare possibility might lead to a misinterpretation of such metastases as a primary tumor of the minor salivary glands and result in excessive treatments. According to Western literature, the most common primary sites of oral/oropharyngeal metastases are the lung, kidney, and prostate for men, and the breast, female genital organs, and kidney for women.3 Metastatic tumors tend to involve the jaw bone more often than the oral soft part (2:1 ratio, respectively).3 Lim et al.4 metaanalyzed cases of 41 metastatic tumors in the jaws and the oral soft part that were reported in Korea. Collectively, the most common primary site was the liver (27.8%) for males and the female genital organs (16.7%) for females; the jaw bone was also more involved than the oral soft part (1.3:1 ratio, respectively).4 Roh et al.5 reported a 0.05% occurrence of head and neck metastases among 12,602 Korean patients with hepatocellular carcinoma (HCC). We separated the oral/oropharyngeal location from the sinonasal tract, of which metastases were previously studied,6 and analyzed oral cavity/oropharynx cancers in a 16 year period from one institute to reveal the incidence, primary sites, clinical manifestations, pathologic features, and prognosis of metastatic tumors to the oral cavity and oropharynx.

Head and neck squamous cell carcinoma (HNSCC) is a clinically challenging disease group with more than 551,000 new cases and over 306,000 deaths worldwide in 2008.1 It is well known that the most important risk factors for HNSCC are tobacco use and alcohol consumption. In addition to these classic risk factors, human papillomavirus (HPV) infection has recently been identified as an independent risk factor for HNSCC, especially of oropharyngeal cancers.2 Interestingly, the incidences of oropharyngeal cancers have been increasing in the US and Korea over the past decade, while those of laryngeal cancers have decreased.3,4 This increasing incidence pattern may be related to an HPV epidemic; however, its relationship with HNSCC in Korean patients has not been clarified. The reported prevalence of HPV in oropharyngeal or tonsillar SCC over the past two decades varies broadly, ranging from 0% to 100%, depending on the location, patient ethnicity, specimen type, and detection method.2,5-10 The clinical significance of this subset has not been completely determined, though HPV-positive HNSCC patients had a tendency to be younger with no history of smoking or alcohol consumption and show a favorable prognosis.11 Also, morphologic characteristics of HPV-positive tumors have been described as non-keratinizing, poorly differentiated, having basaloid morphology with cystic cervical lymph node metastasis, or tonsillar crypt origin.7,8,12,13 The oncogenic HPV disrupts the cell cycle through two viral oncoproteins, E6 and E7, which functionally inactivate p53 and pRb tumor suppressor proteins, respectively. The disruption yields down-regulation of p53, pRb, and cyclin D1 and up-regulation of cyclin-dependent kinase inhibitors p16INK4A, p21CIF1/WAF1, as well as p14ARF. The aims of this study are to identify the prevalence of HPV in tonsillar squamous cell carcinoma (TSCC) from Korea, a low but increasing incidence region, to observe the clinicopathologic features of HPV-associated TSCC and to determine the prognostic values of HPV and related proteins.

A new tumor entity of the salivary gland, mammary analogue secretory carcinoma (MASC) has recently been proposed. The entity was first presented by Skalova et al. in 2010,1 as a distinctive neoplasm with strong similarities to breast secretory carcinoma including ETS variant gene 6 (ETV6)-neurotrophic tyrosine kinase receptor, type 3 (NTRK3) translocation. Since their report, a succession of studies has followed to characterize and distinguish MASC from other salivary gland tumors.1-5 Histologically, the tumors have been reported to show a microcystic, papillary-cystic, glandular, or solid growth patterns, low-grade vesicular nuclei, pale pink granular or vacuolated "bubbly" cytoplasm, and intraluminal or intracellular secretions, featuring subtypes of acinic cell carcinoma (AciCC). According to recent study results, MASCs also mimic other salivary gland tumors, including adenocarcinoma, not otherwise specified (ANOS), mucoepidermoid carcinoma (MEC), and cystadenocarcinoma (CAC).3 Clinically, according to Chiosea et al.,5 MASCs have been known to show a male predilection and more prevalence for non-parotid sites but showed no statistically significant outcome difference, compared to AciCCs. Currently, diagnosing MASCs only by histological features without a molecular study is difficult, and their immunohistochemical characteristics have not been fully investigated. ETV6-NTRK3 fusion gene is expressed in human secretory breast carcinoma. This gene is the product of a t(12;15)(p13;q25) that fuses the dimerization domain of a transcriptional regulator (ETV6) on chromosome 12 with a membrane receptor tyrosine kinase (NTRK3) on chromosome 15 and has also been reported to associate with infant fibrosarcoma, congenital mesoblastic nephroma and acute myelogenous leukemia. ETV6 is genetically unstable, thus susceptible to chromosomal rearrangements, and is implicated in leukemia, myelodysplastic syndromes and sarcomas, fusing with dozens of genes such as ABL1, FGFR3, PAX5, SYK, and JAK2, in addition to NTRK3. ETV6-NTRK3 gene rearrangement has been proven in MASCs as in other epithelial, mesenchymal, or hematopoietic tumors. Recent studies suggested that the inhibition of ETV6-NTRK3 activation could serve as a therapeutic drug for the treatment of patients with this fusion.6,7 This entity is very new, and to date, no case has been documented in Korea. We aimed to retrospectively identify MASCs using fluorescence in situ hybridization (FISH) for ETV6 rearrangement, and define the histological, clinical, and immunohistochemical characteristics.