No detectable hypoxia in malignant salivary gland tumors: preliminary results.

Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type.

A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma.

Two pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation- and cell-cycle-related biomarkers and the presence of high-risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy-five differentiated vulvar intra-epithelial neoplasia (VIN)-lesions with adjacent SCC and 45 usual VIN-lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr-HPV DNA, using a broad-spectrum HPV detection/genotyping assay (SPF(10)-LiPA), and the immunohistochemical expression of MIB1, p16(INK4A) and p53.

Recurrent melanotic neuroectodermal tumor of infancy: a proposal for treatment protocol with surgery and adjuvant chemotherapy.

The case of a 4-month-old male infant treated with combined surgery and chemotherapy for an aggressive recurrent melanotic neuroectodermal tumor of infancy (MNTI) on the top of the alveolar process of the mandible with a long-term follow-up is presented. Initial treatment comprised conservative local excision and curettage of the mandible. After several local recurrences and because radical surgical excision would give gross functional and aesthetic mutilation, finally complete, long-lasting remission was achieved with adjuvant chemotherapy, according to a neuroblastoma protocol (10-year follow-up).

Improved identification of malignant cells in serous effusions using a small, robust panel of antibodies on paraffin-embedded cell suspensions.

Objective: To evaluate the expression of these markers individually and to find out which markers would be the most effective in a diagnostic panel to reliably discriminate these lesions.

Study Design: Sections from cell blocks of these fluids were stained with antibodies against calretinin, EMA, HMFG-2, BerEp4, B72.3 and CEA.

Objective assessment of cancer biomarkers using semi-rare event detection.

Objective and reproducible assessment of cancer biomarkers may be performed using rare event detection systems. Because many biomarkers are not true 'rare events', in this study a semi-rare event detection system was developed. The system is capable of assigning a discriminant score to detected positive cells, expressing the extent and intensity of the immunocytochemical staining.

Multiple complications due to osteoradionecrosis in a patient with thromboangiitis obliterans.

A case is presented of a patient with thromboangiitis obliterans (TAO) who developed severe necrosis of the intraoral soft tissues and maxillary and mandibular bone after radiotherapy for a cT2N0M0 squamous cell carcinoma of the soft palate. Multiple surgical procedures including partial resection of the mandible and maxilla and reconstruction of intraoral and extraoral defects with a pectoralis major myocutaneous flap and anterolateral thigh flap were performed with partial success. Although a causal relationship between TAO and the described complications cannot be verified, close monitoring of patients with TAO who are being treated with radiotherapy is advised.

MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva.

Lichen sclerosus, high-grade usual vulvar intraepithelial neoplasia (VIN) and differentiated VIN have a different malignant potential. The objective of this study was to quantify the proliferative activity in the basal region of the epithelium of vulvar premalignancies. Furthermore, we investigated whether MIB1 expression in the basal region of vulvar epithelium can be helpful in diagnosing differentiated VIN, which may be hard to discern from normal epithelium.

The prognostic value of endogenous hypoxia-related markers for head and neck squamous cell carcinomas treated with ARCON.

Background And Purpose: Hypoxic radioresistance is an important cause for treatment failure in a number of tumor types including head and neck cancers. Recent studies suggest that outcome can be improved by oxygenation modifying treatments such as ARCON. A robust endogenous marker of hypoxia might be a valuable aid to select patients for such treatments.

Treatment results of patients with a squamous cell carcinoma of the buccal mucosa.

The purpose of this study was to evaluate outcome and value of follow-up of squamous cell carcinoma (SCC) of the buccal mucosa in patients treated at the Radboud University Nijmegen Medical Centre, The Netherlands. A longitudinal cohort study was performed involving 32 patients treated with curative intent (surgery on indication followed by radiotherapy) for SCC of the buccal mucosa from 1987 to 2002, with a minimum follow-up of three years. The prognosis of SCC of the buccal mucosa is comparable to other sites of the oral cavity.

p14ARF and p16INK4A, two products of the same gene, are differently expressed in cervical intraepithelial neoplasia.

Objective: To study the expression patterns of two different tumor suppressor proteins p16INK4A and p14ARF in cervical lesions. Both proteins are encoded by the same INK4A/ARF gene on chromosome 9p21. The expression patterns of these two proteins, both playing a central role in the cell cycle, were analyzed in detail in CIN, carcinomas, and normal epithelium to test the hypothesis that p16INK4A positive cells also demonstrate p14ARF expression.

Effectiveness of routine follow-up of patients treated for T1-2N0 oral squamous cell carcinomas of the floor of mouth and tongue.

Background: The duration of follow-up after treatment for head and neck cancer, the depth of the routine visits, and the diagnostic tools used are determined on the basis of common acceptance rather than evidence-based practice. Patients with early-stage tumors are more likely to benefit from follow-up programs, because they have the best chance for a second curative treatment after recurrence. The purpose of this study was to determine the benefit of our 10-year follow-up program in patients with stage I and II squamous cell carcinoma (SCC) of the floor of mouth and tongue.

Interleukin-12 has no effect on vascular density, perfusion, hypoxia and proliferation of an implanted human squamous cell carcinoma xenograft tumour despite up-regulation of ICAM-1.

Background: Interleukin-12 is an anti-angiogenic and antitumor agent in many transplanted murine tumour models. In a previous clinical study in head and neck squamous cell carcinoma patients treated with rhIL-12 the tumour turned pale, after an initial reddening. The aim of this study was to investigate the effects of rmIL-12 on the vasculature, blood perfusion, hypoxia and proliferation of tumour cells in an implanted human head and neck squamous cell carcinoma xenograft tumour, with a relatively large diameter, in Balb/c nu/nu mice over time.

Intratumoral recombinant human interleukin-12 administration in head and neck squamous cell carcinoma patients modifies locoregional lymph node architecture and induces natural killer cell infiltration in the primary tumor.

The objective of this study was to evaluate the histologic and immunohistopathologic effects of intratumorally given recombinant human interleukin-12 on the immune cells in the primary tumors and regional lymph nodes. Ten previously untreated patients with head and neck squamous cell carcinoma (HNSCC) were injected in the primary tumor twice to thrice, once weekly, at two dose levels of 100 or 300 ng/kg, before surgery. These patients were compared with 20 non-IL-12-treated control HNSCC patients.

INK4-ARF and p53 mutations in metastatic cutaneous squamous cell carcinoma: case report and archival study on the use of Ink4a-ARF and p53 mutation analysis in identification of the corresponding primary tumor.

So far, histopathologic, immunohistochemical and molecular properties of metastatic cutaneous squamous cell carcinomas (CSCCs) are relatively unexplored. In patients with multiple CSCCs, as for instance renal transplant recipients (RTRs), it might prove difficult to identify the primary tumor responsible for metastasis. We report a case of an RTR with multiple CSCCs, one of which metastasized.

Quantitation of Ki-67 expression in the differential diagnosis of reserve cell hyperplasia vs. small cell lung carcinoma.

Objective: To investigate whether the detection of proliferation-associated Ki-67 antigen may be of value in differentiating between reserve cell hyperplasia (RCH) and small cell lung cancer (SCLC).

Study Design: Retrospectively, 20 Papanicolaou-stained bronchial brushes or washings from 20 patients were selected. Ten were diagnosed as RCH (and had no SCLC in follow-up) and the other 10 as SCLC (histologically confirmed).

Rational approach to diagnosis and treatment of ameloblastomas and odontogenic keratocysts.

We present decision trees on the treatment of cystic lesions of the jaws based on their location. We give special consideration to the treatment of potentially aggressive lesions such as odontogenic keratocysts and cystic ameloblastomas. The treatment plan is based on a retrospective study of 19 ameloblastomas and similar published studies combined with a prospective study of keratocysts.

Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-helper 1 profile in the locoregional lymph nodes.

The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients.

Different chromosomal imbalances in metastasized and nonmetastasized tongue carcinomas identified by comparative genomic hybridization.

Tumors of different metastatic behavior possibly differ in genomic constitution. We identified molecular cytogenetic differences between a group of metastasized and nonmetastasized primary tongue tumors by comparative genomic hybridization. Most frequent chromosome copy number changes for metastasized and nonmetastasized tumors were +8q (100% and 71%, respectively) and +3q (56% and 43%, respectively).

P16 and p53 expression in (pre)malignant epidermal tumors of renal transplant recipients and immunocompetent individuals.

Ultraviolet (UV) radiation is a prevailing factor implicated in the etiology of keratinocytic intraepidermal neoplasia (KIN) and squamous cell carcinomas (SCCs), as evidenced by the high frequency of UV-related mutations in the p53 and p16 tumor suppressor genes. In renal transplant recipients (RTRs), immunosuppression is considered another important risk factor in the enhanced carcinogenesis in these patients. So far, effects of UV and immune status on p53 and p16 immunoexpression in SCCs and precursors have not been studied.

Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer.

Hypoxia is associated with tumor aggressiveness and is an important cause of resistance to radiation treatment. Assays of tumor hypoxia could provide selection tools for hypoxia-modifying treatments. This study correlated the exogenous 2-nitroimidazole hypoxia marker 1-[(2-hydroxy-3-piperidinyl)propyl]-2-nitroimidazole hydrochloride (pimonidazole) with the endogenous hypoxia-related marker carbonic anhydrase 9 (CA9) and with vascular parameters using immunohistochemical techniques and a computerized image analysis system.

Numerical aberrations of chromosome 1 in cervical intraepithelial neoplasia are strongly associated with infection with high-risk human papillomavirus types.

The aims of this study were to assess the relationships between numerical aberrations of chromosome 1 and the presence of high-risk human papillomavirus (HPV). Five normal samples, 11 CIN1, 13 CIN2, 18 CIN3, and nine carcinomas were studied by in situ hybridization (ISH), using a DNA probe for the centromere of chromosome 1 (cen#1) and a DNA probe cocktail for HPV types 16 and 18. A short fragment polymerase chain reaction hybridization line probe assay (SPF-PCR-LiPA) technique was used to detect 25 HPV types.

Computer assisted analysis of the microvasculature in metastasized and nonmetastasized squamous cell carcinomas of the tongue.

Background: Quantification of microvessels in solid malignancies is regarded as a potential test to predict their clinicobiologic behavior. However, discordant results have been reported for head and neck cancer that may be explained by varying methods.

Methods: In this retrospective study, we therefore quantified the microvasculature in 20 nonmetastasized and 20 metastasized squamous cell carcinomas of the tongue, using recently developed methods.

Markers for nodal metastasis in head and neck squamous cell cancer.

Objective: To identify markers that are relevant as predictors of lymph node metastasis in head and neck squamous cell cancer.

Design: Expression of p53, Rb, cyclin D1, E-cadherin, and epithelial cell adhesion molecule was examined using immunohistochemical analysis and traditional histological parameters, and the correlation of these markers with the histologically verified presence of regional metastases was determined.

Subjects: The study sample comprised 121 patients with head and neck squamous cell cancer from whom paraffin-embedded material of primary tumors was used.