RESUMO
BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC. METHODS: Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations. RESULTS: The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations. CONCLUSIONS: The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.
RESUMO
Axillary lymph node (ALN) metastasis is a key step of tumor progression in breast cancer and is associated with an unfavorable prognosis. However, the mechanisms of this process are not well understood. Proteomic technologies have led to identification of specific protein markers and a better understanding of the cellular processes. To explore this, differential protein expression was analyzed between node-positive breast carcinoma and node-negative breast carcinoma (11 samples) and between primary breast carcinoma and matched metastatic ALN (five pairs) using a combination of 2D-SDS-PAGE and LC-MC/MS. Of the total 678 protein spots, 19 proteins were up-regulated and 3 proteins were down-regulated in node-positive breast carcinomas compared to node-negative breast carcinomas. Four up-regulated proteins were identified, namely annexin 5, carbonic anhydrase I, peroxiredoxin 6 and proteasome α2 subunit. For proteins altered in metastatic ALN compared to primary tumors, 6 of 14 up-regulated proteins were identified: heat shock 70 kDa protein 5, protein disulfide isomerase, prolyl 4-hydroxylase ß subunit precursor, lactate dehydrogenase B, triosephosphate isomerase 1 and ß-tubulin and 5 of 23 down-regulated proteins were identified including 90 kDa heat shock protein, chain A apo-human serum transferrin, chain A α1-antitrypsin, enolase 1 and macrophage migration inhibitory factor. Immunohistochemistry showed stronger immunostaining for ß-tubulin in metastatic ALN compared to primary breast tumor. All of the identified proteins function in various processes involved in cell survival and growth. Our results suggest that these processes are critical for tumor progression and metastasis and the proteins identified could be candidate markers of clinical usefulness.