Sven Saussez

Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases

PurposeBisphosphonates (BPs) are bone-remodeling inhibitors that are used to manage bone metastases and osteoporosis. Osteonecrosis of the jaw, however, can occur during treatment. This complication is poorly understood and is called “bisphosphonate-induced osteonecrosis of the jaw” (BIOJ).MethodsWe performed a PubMed-based review of all of the described cases of BIOJ from January 2003 (the year of the first description) to September 2009. Issues of clinical relevance, such as the primary diagnosis and type of treatment, were evaluated for each patient case.ResultsWe retrieved 2,408 cases, 88% of which were associated with intravenous therapy, primarily with zoledronate. Of the total number of cases, 89% were associated with the treatment of a malignant condition, particularly multiple myeloma (43% of the cases). Of all the BIOJ cases, 67% were preceded by tooth extraction and only 35% of patients were cured.ConclusionPrevention is better than treatment, and the establishment of meticulous oral hygiene and surgical procedures prior to commencing BP treatment is important for preventing BIOJ. Our review summarizes the current knowledge about this severe complication. Future studies, especially basic research studies, are needed to better understand this devastating disease.

Immune Suppression in Head and Neck Cancers: A Review

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be link to the fact that HNSCCs strongly influence the host immune system. We present a critical review of our understanding of the HNSCC escape to the antitumor immune response such as a downregulation of HLA class I and/or components of APM. Antitumor responses of HNSCC patients are compromised in the presence of functional defects or apoptosis of T-cells, both circulating and tumor-infiltrating. Langerhans cells are increased in the first steps of the carcinogenesis but decreased in invasive carcinomas. The accumulation of macrophages in the peritumoral areas seems to play a protumoral role by secreting VEGF and stimulating the neoangiogenesis.

Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer.

BackgroundEighty percent of hypopharyngeal squamous cell carcinoma patients have advanced stages (III and IV) of the disease, and biological markers are required to predict high-risk head and neck squamous cell carcinoma patients in need of highly aggressive treatments after surgery to improve the survival rate. We analyzed the potential prognostic value of galectin 7 in a series of 81 stage IV hypopharyngeal SCCs because galectin 7 is an emerging marker involved in the epidermal development of pluristratified epithelia and in epidermal cell migration.MethodsThe immunohistochemical expression of galectin 7 was determined on a series of 81 stage IV hypopharyngeal SCCs and was compared with that of galectins 1 and 3.ResultsHigh levels of galectin 7 expression were associated with rapid recurrence rates and dismal prognoses in these 81 stage IV hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed weakly, if at all, with galectin 1.ConclusionsThese data suggest that the immunohistochemical determination of galectin 7 expression in the case of high-risk hypopharyngeal cancers is a meaningful tool to identify patients who should benefit from aggressive postsurgical adjuvant therapy after surgery, including not only radiotherapy, but also chemotherapy.

Increased expression and altered intracellular distribution of adhesion/growth‐regulatory lectins galectins‐1 and ‐7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas

Aims: To examine the level of expression of the pleiotropic regulators galectins‐1 and ‐7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas.

Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.

The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients.

High incidence of high-risk HPV in benign and malignant lesions of the larynx

The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup.

Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: a Belgian case series.

Bisphosphonate‐related osteonecrosis of the jaw (BROJ) is a serious oral complication of bisphosphonate (BP) treatment involving the exposure of necrotic maxillary or mandibular bone. Our purpose is to describe the clinical presentation of 34 cases of BROJ and to identify potential risk factors.

Galectins as modulators of tumor progression in head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) remain a significant cause of morbidity worldwide. Biological therapies able to induce and/or upregulate antitumor immune responses could represent a complementary approach to conventional treatments for patients with HNSCC because, despite advances in surgery, radiotherapy, and chemotherapy, the overall survival rates for these patients have not changed over recent decades. Galectins are involved in the control of cell proliferation, cell death, and cell migration and in the modulation of various functions of the immune system. In this context, galectin‐1 is known to protect HNSCCs from the immune system. The present review details the involvement of galectins in HNSCC biology and suggests a number of approaches to reduce the levels of expression of galectin‐1 in HNSCCs, with the aim of improving the efficiency of HNSCC immunotherapy.

The Helicase-Like Transcription Factor and its implication in cancer progression

Abstract.The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of chromatin-remodeling factors. Several SWI/SNF genes are disrupted in cancer, suggesting their possible role as tumor suppressors. Similarly, the HLTF gene was found to be inactivated by hypermethylation in a significant number of colon, gastric and uterine tumors, indicating that HLTF silencing may confer a growth advantage and that HLTF could be considered as a tumor suppressor gene. However, 20-fold HLTF overexpression was detected in various transformed cell lines, suggesting that HLTF could be associated with neoplastic transformation and act more like an oncogene. Moreover, HLTF activation was recently linked to the initial steps of carcinogenesis in an experimental model of estrogen-induced kidney tumors. Those apparently contradictory observations suggest that HLTF might play various roles in cancer. In this review, we will try to reconcile all these data in order to specify the role of HLTF in cancer progression.

Thyroid tumor marker genomics and proteomics: diagnostic and clinical implications.

Two systems biology concepts, genomics and proteomics, are highlighted in this review. These techniques are implemented to optimize the use of thyroid tumor markers (TTM). Tissue microarray studies can produce genetic maps and proteomics, patterns of protein expression of TTM derived from preoperative biopsies and specimens. For instance, papillary and medullary thyroid cancers harbor RAS, RET, and BRAF genetic mutations. Follicular thyroid cancers harbor translocations and fusions of certain genes (PAX 8 and PPAR‐gamma). Proteomic analysis from various tissue sources can provide useful information regarding the overall state of a thyroid cancer cell. Understanding the molecular events related to these genetic and protein alterations can potentially clarify thyroid cancer pathogenesis and guide appropriate molecular targeted therapies. However, despite the realization that these emerging technologies hold great promise, there are still significant obstacles to the routine use of TTM. These include equivocal thyroid nodule tissue morphologic interpretations, inadequate standardization of methods, and monetary costs. Interpretative shortcomings are frequently due to the relative scarcity of cellular material from fine‐needle aspiration biopsy (FNAB) specimens. This can be rectified with large needle aspiration biopsy (LNAB) techniques and is exemplified by the favorable performance of galectin‐3 determinations on LNAB specimens. J. Cell. Physiol. 224: 612–619, 2010.