Advances in molecular mechanisms of bone invasion by oral cancer / 华西口腔医学杂志

Bone invasion by oral cancer is a common clinical problem, which affects the choice of treatment and predicts a poor prognosis. Unfortunately, the molecular mechanism of this phenomenon has not been fully elucidated. Current studies have revealed that oral cancer cells modulate the formation and function of osteoclasts through the expression of a series of signal molecules. Many signal pathways are involved in this process, of which receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway attracted much attention. In this review, we introduce recent progress in molecular mechanisms of bone invasion by oral cancer.

Role of proteases, cytokines, and growth factors in bone invasion by oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy and an increasing global public health problem. OSCC frequently invades the jaw bone. OSCC-induced bone invasion has a significant impact on tumor stage, treatment selection, patient outcome, and quality of life. A number of studies have shown that osteoclast-mediated bone resorption is a major step in the progression of bone invasion by OSCC; however, the molecular mechanisms involved in OSCC bone invasion are not yet clear. In this review, we present the clinical types of OSCC bone invasion and summarize the role of key molecules, including proteases, cytokines, and growth factors, in the sequential process of bone invasion. A better understanding of bone invasion will facilitate the discovery of molecular targets for early detection and treatment of OSCC bone invasion.

Vestibular Schwannoma Atypically Invading Temporal Bone

Vestibular schwannoma (VS) usually present the widening of internal auditory canal (IAC), and these bony changes are typically limited to IAC, not extend to temporal bone. Temporal bone invasion by VS is extremely rare. We report 51-year-old man who revealed temporal bone destruction beyond IAC by unilateral VS. The bony destruction extended anteriorly to the carotid canal and inferiorly to the jugular foramen. On histopathologic examination, the tumor showed typical benign schwannoma and did not show any unusual vascularity or malignant feature. Facial nerve was severely compressed and distorted by tumor, which unevenly eroded temporal bone in surgical field. Vestibular schwannoma with atypical invasion of temporal bone can be successfully treated with combined translabyrinthine and lateral suboccipiral approach without facial nerve dysfunction. Early detection and careful dissection of facial nerve with intraoperative monitoring should be considered during operation due to severe adhesion and distortion of facial nerve by tumor and eroded temporal bone.

Expressão imuno-histoquímica de proteínas relacionadas com a absorção óssea em carcinoma epidermoide de palato duro e língua / Immunohistochemical expression of proteins related to bone resorption in squamous cell carcinoma of the hard palate and tongue

O carcinoma epidermóide oral (CEO) apresenta uma tendência marcante de invadir o osso quando localizado em palato duro e rebordo. O mecanismo preciso desta invasão permanece incompletamente descrito, apesar de sugerirem na literatura que a destruição óssea, invasão e metástase seja mediada por osteoclastos e não diretamente por células do carcinoma. As moléculas RANK/RANKL /OPG são fundamentais na oesteoclastogênese, assim como a IL-6 que regula suas expressões. O objetivo desta pesquisa foi avaliar a expressão imuno-histoquímica de fatores de reabsorção óssea (RANKL e OPG) e da citocina (IL-6) no carcinoma epidermóide de palato duro (com invasão óssea) e língua (sem invasão óssea), correlacionandoas com os parâmetros clinicopatológicos e prognósticos. A amostra foi constituída por 30 carcinomas epidermóides com invasão óssea (localizados no palato) e 31 sem invasão óssea (localizados na língua). Foram avaliados a intensidade e a média das células tumorais, estromais e inflamatórias imunomarcadas para os anticorpos anti-RANKL, anti-OPG e anti-IL-6, no front de invasão e no centro tumoral. O escore (s) da imunorreatividade das células foi estabelecido através da multiplicação do percentual de células positivas (P) pelo valor da intensidade da marcação (I) (S = P x I), em cinco campos (400×). A análise da expressão da proteína RANKL foi significativamente mais expressa (p=0,002) nas células inflamatórias, com tendência há uma maior expressão nas células dos carcinomas epidermóides do palato duro. Entre os parâmetros clinicopatológicos foi observado associação do RANKL com o pior prognóstico, com significância estatística apenas para o estágio avançado do tumor (p= 0,033). A OPG demonstrou fraca expressão tanto nos casos de língua (0,77 ±1,85) quanto de palato duro (1,32 ± 2,48), com ausência de significância estatística (p>0,05). Em relação aos parâmetros clinicopatológicos a OPG apresentou tendência de associação com o pior prognóstico, com associação estatística significante para o óbito (p=0,048) e invasão perivascular (p=0,047). A IL-6 foi significantemente mais expressa (p<0,001) em células tumorais e inflamatórias nos carcinomas epidermóides de palato duro. E dentre os parâmetros clinicopatológicos, a IL-6 apresentou tendência de associação com o bom prognóstico, com diferença estatística para a ausência de metástase e as células tumorais (p = 0,020), estromais (p = 0,027) e inflamatórias (p = 0,017). Com base nos resultados pode-se concluir que a IL-6 pode ser utilizada como um marcador do carcinoma epidermóide oral com invasão óssea, e que a relação RANKL/OPG está alterada no carcinoma epidermóide oral. (AU)

Oral squamous cell carcinoma (CEO ) has a marked tendency to invade the bone when located in the palate and lip . The precise mechanism of this invasion is still not completely described , although the literature suggests that the bone destruction ABSTRAT , invasion and metastasis is mediated by osteoclasts and not directly by carcinoma cells . The molecules RANK / RANKL / OPG are fundamental in oesteoclastogênese, and IL-6 that regulates its expression. The objective of this research was to evaluate the immunohistochemical expression of factors of bone resorption ( RANKL and OPG ) and cytokine ( IL - 6 ) in squamous cell carcinoma of the hard palate (with bone invasion ) and tongue (without bone invasion ) , correlating with the clinicopathological parameters and prognosis. The sample consisted of 30 squamous cell carcinoma with bone invasion (located on the palate) and 31 without bone invasion (located on the tongue). Were evaluated and the average intensity of the tumor cells , stromal and inflammatory immunostained for anti-RANKL antibodies , anti- OPG and anti -IL- 6 at the invasive front and center of the tumor. The score (s) of the immunoreactivity of cells was established by multiplying the percentage of positive cells (P) for marking intensity value (I) (S = P x I) in five fields (× 400). The analysis of the expression of RANKL protein was expressed significantly higher (p = 0.002) in inflammatory cells, there is a trend to higher expression in squamous cell carcinomas of the hard palate. Among the clinicopathologic parameters was observed association of RANKL with the worst prognosis, with statistical significance only for the advanced stage of the tumor (p = 0.033). The OPG showed weak expression both in cases of tongue (0.77 ± 1.85) and hard palate (1.32 ± 2.48), with no statistical significance (p > .05). In relation to clinicopathological parameters OPG tended association with worse prognosis, with a statistically significant association for death (p = 0.048) and perivascular invasion (p = 0.047). IL- 6 was expressed significantly more (p < 0.001) in tumor and inflammatory cells in squamous cell carcinoma of the hard palate. In addition, among the clinicopathologic parameters, IL- 6 showed a tendency of association with good prognosis, with a statistical difference for the absence of metastasis and tumor cells (p = 0.020), stromal (p = 0.027) and inflammatory (p = 0.017). Based on the results it can be concluded that IL -6 may be used as a marker of oral squamous cell carcinoma with bone invasion, and the ratio RANKL / OPG is changed in oral squamous cell carcinoma. (AU)

Giant Acral Melanoma on the Left Thumb of a Korean Patient

The acral regions of the limbs of Asians are predisposed to develop malignant melanoma, but giant-sized acral melanoma has not been previously reported in the Asian population. Giant-sized melanoma implies aggressive tumor invasion and so it is more difficult to achieve a therapeutic cure. A 56-year-old woman presented with a giant acral melanoma of the left thumb with concomitant bone destruction and axillary lymph node metastasis. The initial lesion was a subungual black macule on the left thumb that had grown into a giant 7.0*4.0*3.5 cm-sized melanoma over a 3 year period. The left thumb was amputated and the axillary lymph nodes were completely dissected. During the ensuing 3 months, she underwent adjuvant treatment with interferon-alpha-2a. The interesting feature of this case is that the large melanoma mass of this patient, which was accompanied with adjacent bone destruction and lymph node metastasis, had developed rapidly from a small black macule in the nail matrix, and this black macule was suspected to be a subungual melanoma.