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Biomedical subjects

Lisa Licitra

Publications and source records attributed to Lisa Licitra.

At least 19 recordsLinked to original sources
PubMed2006

High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma.

PURPOSE: Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear. PATIENTS AND METHODS: To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery. RESULTS: Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves. CONCLUSION: Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.

Adult↗
PubMed2006

Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. EXPERIMENTAL DESIGN: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. RESULTS: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. CONCLUSIONS: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.

Biomarkers, Tumor↗
PubMed2006

Systemic therapy in the palliative management of advanced salivary gland cancers.

Cancers of the salivary glands are unusual lesions that vary widely in their histologic appearance and molecular characteristics. Likewise, there is a wide spectrum of biologic behavior, ranging from low-grade, minimally invasive tumors, to highly lethal malignancies. There are few data on the role of systemic therapies in the management of these cancers, and chemotherapy is generally reserved for the palliative management of advanced disease that is not amenable to local therapies such as surgery and/or radiation. The majority of patients for whom systemic therapy is considered will have either adenoid cystic carcinoma, mucoepidermoid carcinoma, or high-grade adenocarcinoma. This article will review the available literature regarding the use of palliative chemotherapy for patients with advanced salivary gland cancer of these histologies, with an emphasis on the potential role of targeted agents. There is a need for a determined, coordinated effort to conduct high-quality clinical trials in patients with these rare cancers.

Adenocarcinoma↗
PubMed2006

Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.

BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses shows microscopic features indistinguishable from colorectal cancer. Our aim was to verify whether the morphologic resemblances mirror genetic profile similarities. METHODS: Twenty consecutive surgically treated ITAC cases, previously investigated for p16(INK4a) and TP53, were investigated for hMLH1, hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations. RESULTS: One case was immunonegative for both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong beta-catenin overexpression. No BRAF and APC truncating mutations were identified, whereas K-ras mutations were detected in 9 ITACs (50%). CONCLUSIONS: Our data confirm the phenotypic similarities at the genetic level between colorectal cancer and ITACs showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome 18q. By contrast, both frequency rate and type of inactivation of the APC-beta-catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in the early development of ITAC (p16(INK4a) and TP53) and colorectal cancer (APC).

Adaptor Proteins, Signal Transducing↗
PubMed2006

A multidisciplinary approach to squamous cell carcinomas of the head and neck: what is new?

PURPOSE OF REVIEW: The aim of this article is to review progress in the treatment of head and neck squamous cell carcinomas (in the light of the most recent literature). Due to the complexity of the disease the multidisciplinary approach needs also a multidisciplinary knowledge which this review tries to summarize. RECENT FINDINGS: The multidisciplinary treatment approach to the disease includes predictive and prognostic value of biomolecular and clinical factors, the role of induction chemotherapy and concurrent chemo-radiotherapy, new advances in postoperative treatment, treatment-related side-effects and their impact on patients' quality of life, new targeted therapies and treatment choice for incurable patients. Advances in other disciplines, such as radiation therapy and new imaging techniques, will be considered elsewhere in this journal. SUMMARY: Major advances derived from the strategic use of different treatment and diagnostic modalities. The importance of a multidisciplinary team and knowledge in the approach of this disease should be stressed. Today, a multidisciplinary diagnostic and treatment philosophy is the tool to guarantee the best treatment plan definition, to prevent and relieve treatment adverse effects with the ultimate goal to improve survival.

Carcinoma, Squamous Cell↗
PubMed2006

Advances in the changing patterns of aetiology of head and neck cancers.

PURPOSE OF REVIEW: Recent cumulated evidence suggests that factors other than those conventionally known may contribute to the development of head and neck cancer. In fact, a review of the most recent literature shows interesting advances in molecular epidemiology. RECENT FINDINGS: Recent studies have pointed out the role both of exposure to carcinogens and of an inherited or acquired genetic susceptibility. A very broad mechanism by which gene families can be responsible for the disease has been depicted. This mechanism ranges from behaviour genes, which can regulate lifestyle habits, to metabolizing genes, DNA repair genes and cell cycle control genes. SUMMARY: This review tries to summarize the most recent advances in the field of cancerogenesis in head and neck cancer.

Alcohol Drinking↗
PubMed2005

Which classification for ethmoid malignant tumors involving the anterior skull base?

BACKGROUND: The purpose of this study was to compare three systems of classification for malignant ethmoidal tumors in patients undergoing anterior craniofacial resection. METHODS: A radiologic locoregional evaluation of 241 patients with malignant ethmoid tumors was performed before patients underwent an anterior craniofacial resection. Disease in each case was staged according to the American Joint Committee on Cancer-Union Internationale Contre le Cancer (AJCC-UICC) 1997 classification, the AJCC-UICC 2002 classification, and the Istituto Nazionale Tumori (INT) classification. Kaplan-Meier curves and Cox models were used to investigate the prognostic value of each classification system on disease-free survival (DFS) and overall survival (OS). The classifications were compared in terms of prognostic discrimination capability, measured by use of an index of agreement between each classification and DFS or OS time. RESULTS: All three classification systems yielded statistically significant results in the Cox analysis, both for DFS and OS. In the AJCC-UICC 2002 system, minor differences were observed between T1 and T3 tumors. The INT classification showed a progressive worsening of the prognosis with increasing stage. The index of prognostic discrimination favored the INT classification over both the 1997 and 2002 AJCC-UICC classifications. CONCLUSIONS: Both the 1997 and 2002 AJCC-UICC classifications seemed to have limited prognostic value. By contrast, the INT classification satisfied one of the main goals of tumor staging, demonstrating the progressive worsening of prognosis with different tumor classes.

Adolescent↗
PubMed2005

Lung metastasectomy in adenoid cystic carcinoma (ACC) of salivary gland.

To define the role of surgical management of lung metastases in ACC. Twenty ACC patients referred to lung metastasectomy were retrospectively reviewed. Twenty-six operations were performed; at the first metastasectomy, a resection with clear margins (R0) was achieved in 11 patients (55%), 3 are alive and well. Four out of 9 patients with residual disease (R2) are still alive. Median survival after metastasectomy was 78 and 52 months for R0 and R2 (p=0.4); median freedom from progression (FFP) in R0 and R2 groups was 30 and 15 months (p=0.2), respectively. A better outcome was obtained for patients with a disease-free interval 36 months and 6 metastases and bilateral involvement were critical in achieving a R0 intervention. Lung metastasectomy provided a prolonged FFP in a high selected subset of patients with ACC. However, if this could be translated into a survival benefit, it is still to be demonstrated.

Adult↗
PubMed2004

Head and neck tumors other than squamous cell carcinoma.

PURPOSE OF REVIEW: This review deals with classification and treatment of some rare nonsquamous cell carcinomas of the head and neck. RECENT FINDINGS: Paranasal sinus tumor classification is under evaluation. Contrary to the past, the recent tendency is to build stage classifications on prognostic factors that mainly reflect limitations for adequate surgery, and not simply on dimensional criteria, which are more frequently used in TNM. Among sinonasal tract tumors new pathologic entities have been described. So far, little is known about their natural history and about the need to use pathologic classification to differentiate treatment. Recent advances in radiotherapeutic techniques, such as intensity-modulated radiotherapy, will probably have an impact on future treatment of paranasal sinus tumors. Several molecular targets (c-kit, HER-2/neu, androgen receptors) have been identified in salivary gland cancer. It is interesting to note that among different histotypes there is a trend toward a consistent expression of specific markers in specific cancers, suggesting a possible implication of them in the disease histogenesis. Not surprisingly these findings prompted clinical research with molecular targeted drugs. SUMMARY: Nonsquamous cell carcinomas of the head and neck are rare neoplasms. A multidisciplinary team treatment plan is needed, in particular for skull base-located tumors. Salivary gland cancer displays several molecular targets that need to be investigated further.

Carcinoma, Adenoid Cystic↗
PubMed2003

TP53, p14ARF, p16INK4a and H-ras gene molecular analysis in intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.

Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses is an uncommon tumor associated with occupational exposure to dusts of different origin. Few investigations addressed molecular alterations in ITAC mainly focused on TP53, K-ras and H-ras gene mutations. The occurrence of TP53, p14(ARF) and p16(INK4a) deregulation and H-ras mutations was investigated in 21 consecutive and untreated ITACs cases, 17 with known professional exposure. No H-ras mutations were found. In patients with known exposure, cumulative evidence of TP53 or p14(ARF) alterations accounted for 88% and the evidence of p16(INK4a) alterations for 65%, respectively. TP53 mutations were present in 44% of the ITACs, consisted of G:C-->A:T transitions in 86%, and involved the CpG dinucleotides in 50% of the cases. LOH at the locus 17p13 and an uncommon high rate of p53 stabilization were detected in 58% and 59% of the cases, respectively. p14(ARF)and p16(INK4a) promoter methylation accounted for 80% and 67% respectively, and LOH at the locus 9p21 occurred in 45% of the cases. Interestingly, all dust-exposed tumors with p16(INK4a) alterations shared TP53 or p14(ARF) deregulation. The present results show a close association of this occupational tumor with TP53, p14(ARF) and p16(INK4a) gene deregulation. Given the important role that these genes play in cell growth control and apoptosis, the knowledge of ITAC genetic profile may be helpful in selecting more tailored treatments.

Adenocarcinoma↗
PubMed2003

Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial.

PURPOSE: Prognosis of patients with advanced oral cavity cancer is worth improving. Chemotherapy has been reported to be especially active in oral cavity tumors. Here we repeat the results of a randomized, multicenter trial enrolling patients with a resectable, stage T2-T4 (> 3 cm), N0-N2, M0 untreated, squamous cell carcinoma of the oral cavity. PATIENTS AND METHODS: Patients were randomly assigned to three cycles of cisplatin and fluorouracil followed by surgery (chemotherapy arm) or surgery alone (control arm). In both arms, postoperative radiotherapy was reserved to high-risk patients, and surgery was modulated depending on the tumor's closeness to the mandible. Patients' accrual was opened in 1989 and closed in 1999. It included 195 patients. RESULTS: In the chemotherapy arm, three toxic deaths were recorded. No significant difference in overall survival was found. Five-year overall survival was, for both arms, 55%. Postoperative radiotherapy was administered in 33% of patients in the chemotherapy arm, versus 46% in the control arm. A mandible resection was performed in 52% of patients in the control arm, versus 31% in the chemotherapy arm. CONCLUSION: The addition of primary chemotherapy to standard surgery was unable to improve survival. However, in this study, primary chemotherapy seemed to play a role in reducing the number of patients who needed to undergo mandibulectomy and/or radiation therapy. Variations in the criteria used to select patients for these treatment options may make it difficult to generalize these results, but there appears to be room for using preoperative chemotherapy to spare destructive surgery or radiation therapy in patients with advanced, resectable oral cavity cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Cancer of the nasopharynx.

Nasopharyngeal cancer (NPC) is quite rare throughout Europe, accounting for an annual incidence rate below 1 per 100.000, whereas the highest risk area is South East Asia. A predominant occurrence in males is to be noted. NPC is an etiologically multifactorial disease, most probably involving viral, genetic and environmental factors. Carcinomas of the nasopharynx can be divided into two major histotypes: keratinizing squamous cell carcinomas (WHO-type 1) and non-keratinizing carcinomas (WHO-type 2). The histological type is a prognostic factor and it has a clear impact on the outcome of treatment. Standard therapeutic option for early stages of NPC is radiation, while an integration of radiation therapy and chemotherapy is indicated in more advanced stages.

Humans↗
PubMed2003

Major and minor salivary glands tumours.

Malignant salivary gland tumours are rare. The most common tumour site is the parotid. Aetiologic factors are not clear. Nutrition may be a risk factor, as well as irradiation or an histologically benign tumour occurred at a young age. Painless swelling of a salivary gland should always be considered as suspicious, especially if no sign of inflammation is present. Signs and symptoms related to major salivary gland tumours differ from those concerning minor salivary gland tumours, as they depend on the different location of the salivary gland. Surgical excision represents the standard option in the treatment of resectable tumours of both major and minor salivary glands. Neutron radiation may be a treatment option for inoperable locoregional disease. Surgery, irradiation or re-irradiation are treatment options for local relapse, whereas radical neck dissection is indicated for regional relapses. Metastastic disease may be either treated with radiotherapy or palliative chemotherapy, depending on the site of metastases.

Humans↗
PubMed2003

Cancer of the larynx.

In Europe, laryngeal cancer accounts for only 2-5% of all cancers, the incidence being much higher among males than among females. Smoke and alcohol represent the major behavioural risk factors. Several carcinogens, occupations and vitamin deficiencies have been associated with laryngeal cancer. A genetic susceptibility to environmental risk factors and carcinogens is recognized. Hoarseness is the main symptom for which patients call for medical consultation. Mucosa is the most common histologic site of the primary lesions considered in the present chapter. Nodal involvement, the site and volume of the primary tumour, and some genes expression represent the major prognostic factors. A high death rate for not cancer-related events is to be pointed out. The loco-regional extent of the disease determines the success of cure. Surgery and radiotherapy represent the main therapeutic options. The choice between these two procedures is often controversial.

Female↗
PubMed2002

Cancer of the oropharynx.

Oropharyngeal cancer is a rare tumour. Tobacco use and alcohol consumption are recognised as major risk factors. Several carcinogens, occupational exposures and vitamin deficiencies represent the most significant predisposing factors. A varying host susceptibility to carcinogens can be inferred. Carcinoma of the oropharynx has to be suspected whenever sore throat, odynophagia, and ear-ache are described by the patient. Biopsy is mandatory for the definitive diagnosis. TNM classification is crucial for treatment decision-making, while stage grouping is less important. Prognostic factors are treatment-related. Standard treatment of T1-T2 tumours is radiation therapy, for T3 and T4 tumour treatment options are controversial. More advanced tumours can be treated either with surgery followed by conventional radiotherapy or by combined chemo-radiation. Non-conventional fractionation radiotherapy in combination with chemotherapy may represent a third option. Acute toxicity needs to be managed promptly. Late sequelae are less known. Treatment of such tumours requires a multidisciplinary approach within experienced centres.

Humans↗
PubMed2002

Cancer of the anal region.

Cancer of the anal region represents 3-3.5% of all anorectal tumours. The peak incidence is between 58 and 64 years. Since 1960 an increased incidence among men younger than 45 years, and among women has been observed. The number of women diagnosed with anal canal cancer (7 per 1,000,000 person per years) is twice as much as that of men, while anal margins cancers are more frequent in men (4 per 1,000,000 person per years). Tumour extension determines the different treatment strategies, aiming at definite cure, with a conservative approach. Small tumours can be resected without mutilating surgery, while for larger tumours combination of chemotherapy and radiotherapy is the standard treatment, even though a combination of chemotherapy and radiotherapy has been recently introduced. Long-term quality of life (QOL) scores are acceptable, with the exception of patients who experience severe anal dysfunction.

Anus Neoplasms↗