Ali Namazie

Cyclin D1 Amplification and p16(MTS1/CDK4I) Deletion Correlate With Poor Prognosis in Head and Neck Tumors†

Objectives/Hypothesis Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1‐CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer.

Glandular Carcinoma of the Larynx: The Ucla Experience

Glandular carcinomas of the larynx are rare tumors that constitute less than 1 % of all laryngeal malignancies. A retrospective case review of 12 patients with glandular carcinomas of the larynx is presented to identify patient and tumor characteristics, therapeutic modalities, and treatment outcomes. Ten patients underwent surgical excision of the primary tumor, by either supraglottic laryngectomy, vertical partial laryngectomy, or total laryngectomy. Seven of these patients also received postoperative radiotherapy. After a median follow-up period of 23 months, 7 of the 12 patients (58.3%) died as a result of uncontrolled locoregional disease or distant metastases. The 5-year survival rate was 57% in patients who underwent combination therapy versus 50% for those patients who received surgery alone. Surgical resection is the primary treatment modality used in the majority of cases. Neck dissection is reserved for patients with clinically apparent adenopathy, adenocarcinoma, or high-grade mucoepidermoid carcinoma. Combination therapy with surgical resection and radiotherapy may be more effective in achieving tumor remission than is surgical resection alone.

Malignant melanoma of cervical and parotid lymph nodes with an unknown primary site

Forty‐six patients with malignant melanoma metastatic to cervical or parotid lymph nodes with an unknown primary site were treated at UCLA Medical Center from 1964 through 1991. Treatment consisted of parotidectomy and/or neck dissection with or without adjuvant therapy. The initial presentation was a cervical mass in 74% and a parotid mass in 26% of patients. Metastasis distal to the head and neck nodal basins developed in 22% of patients.

Adenoid Cystic Carcinoma of the Base of the Tongue

A retrospective review of 14 patients with adenoid cystic carcinoma of the tongue treated between 1955 and 1997 was performed. Treatment consisted of surgery (n = 2), radiotherapy (n = 2), chemotherapy (n = 1), or combination therapy (n = 9). The 2-, 5-, and 10-year absolute survival rates were 92%, 79%, and 63%, respectively. Seventy-five percent of the patients who died of cancer succumbed to distant metastases. However, long-term survival was common despite a high incidence of local and distant recurrence. The presence of positive surgical margins, the incidence of regional metastases, the incidence of perineural invasion, the initial stage of disease, and the eventual development of locoregional recurrence and distant metastases did not significantly alter the survival rate. Surgical extirpation combined with postoperative radiotherapy is advocated for the treatment of adenoid cystic carcinoma of the tongue. Given the indolent nature of this disease process, surgery should be directed toward conservation of speech and swallowing function.

Clinical application of fluorescence in situ hybridization for chromosome 11q13 analysis in head and neck cancer

Objective: Squamous cell carcinoma of the head and neck (HNSCC) still has one of the lowest 5‐year survival rates. Despite advances in diagnosis, treatment, and research, survival rates have not improved in recent years. This report examines the utility of fluorescence in situ hybridization (FISH) in detecting chromosome 11q13 amplification in HNSCC and in evaluating the correlation between 11q13 amplification and tumor behavior. Study Design: This study used FISH to determine the incidence of 11q13 amplification in 20 HNSCCs and 10 normal controls from the same patients. Tumor touch preparations and paraffin‐embedded tissues from the same patient samples were used for comparative analysis. Both single and dual color FISH was performed. Methods: Repetitive chromosome 11 specific alpha satellite DNA probe and chromosome 11q13 specific probe cyclin D1 were used for the FISH analysis. Results: Experiments revealed amplification of chromosome 11q13 in three fresh touch preparations. FISH on paraffin tissues showed amplification in two additional samples. Intensity of amplification, as high as 20 copies per nucleus, was observed in paraffin preparations, whereas a maximum of only six copies was seen in fresh preparations. Amplification was not detected in any of the normal samples. All five cases with 11q13 amplification had metastases and four of these were from poorly differentiated tumors. In the nonamplified cases, 5 of 15 had metastases and 2 of 15 was poorly differentiated. Conclusions: The present study indicates that FISH is a useful technique for detecting molecular changes such as amplification of chromosome 11q13 in HNSCC. FISH in paraffin preparations allows for accurate measurement of intensity of amplification and makes it possible for the evaluation of a large collection of archival material. The data also suggest that 11q13 amplification is correlated with poorly differentiated tumors and metastasis. Thus FISH has the potential to be a valuable diagnostic/prognostic tool in head and neck cancers. Key Words: Head and neck tumors, FISH, chromosome 11q13.

The role of hyperplasia in multiple parathyroid adenomas.

Parathyroid adenoma is the most common cause of primary hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas have been reported to occur in as high as 11% of patients with pHPT. The significant incidence of multiple adenomas with histologic similarities to hyperplasia has raised the possibility that adenoma is a continuation of the hyperplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corresponding normal glandular tissue. Furthermore, we devised a scheme to definitively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable.

Distant lymphatic metastasis from head and neck cancer.

A predictable pattern of metastasis based on tumor histology and site of origin has been well documented for most cancers that arise in the head and neck region. The current study demonstrates that this predictable pattern of metastasis can be significantly impacted by previous therapy, resulting in unusual patterns of metastasis in patients with recurrent tumors. A retrospective case series of 5 patients with head and neck carcinomas who developed metastases to distant lymph nodes is presented. All patients underwent surgery and radiotherapy to the primary tumor and regional lymphatics at the time of their initial treatment. All of the patients developed a local recurrence less than a year before the detection of distant lymphatic metastases. Cytology or excision confirmed metastases to the axillary, inguinal, or anterior intercostal lymph nodes. All of the patients underwent aggressive surgery for attempted cure of the local recurrence shortly before the presence of distant lymphatic metastases was clinically recognized. The metastatic workup of patients with carcinomas of the head and neck frequently includes examination of the regional lymph nodes as well as chest radiography, liver function tests, and serum calcium determination. This evaluation may fail to detect metastases to distant lymph nodes in patients who present with recurrent or second primary cancers. Such patients should undergo careful examination of all major lymph node-bearing regions of the body when being evaluated for the presence of distant metastases.

CURRENT TECHNIQUES IN MIDFACE LIFTING

Midface elevation is an evolving procedure. The current trends toward less manipulation of the midface soft tissues with less visible incisions and use of endoscopic and percutaneous techniques have allowed for the rejuvenation of the facial features of younger patients. The creation of a natural, unoperated, and youthful appearance to the midface are readily accomplished with these newer procedures. For patients with significant facial skin excess, the endoscopic and percutaneous or transblepharoplasty procedures can be combined with a traditional face or neck lift to restore a youthful facial and neck harmony and balance.

Characteristics of an in vivo canine model of phonation with a constant air pressure source

Many previous studies of laryngeal biomechanics using in vivo models have employed a constant air flow source. Several authors have recently suggested that the lung‐thorax system functions as a constant pressure source during phonation. This study describes an in vivo canine system designed to maintain a constant peak subglottic pressure (Psub) using a pressure‐controlling mechanism.

Fluorescence in situ hybridization for detecting TP16MTS1/CDK41 gene deletions in squamous cell carcinoma of the head and neck

Abstract We have previously shown TP16 MTS1/CDK41 gene deletion in more than 50% of a cohort of squamous cell carcinoma of the head and neck (SCCHN) patients using polymerase chain reaction (PCR). We have performed fluorescence in situ hybridization (FISH) on paraffin-embedded SCCHN specimens from the same cohort to identify the deletion of TP16 MTS1/CDK41CDK41 gene. Twenty normal and 19 SCCHN specimens were studied. An α-satellite DNA probe specific for chromosome 9 and a cosmid probe for the TP16 MTS1/CDK41CDK41 gene were used. Of the 19 tumors examined by FISH, 6 had homozygous deletions, 7 were hemizygously deleted, and the remaining 6 showed no evidence of deletion of the TP16 MTS1/CDK41 gene. None of the normal specimens showed TP16 gene deletion. Data obtained from FISH highly correlated with the PCR results for the identification of TP16 MTS1/CDK41 gene deletions. Patients with deletion of the TP16 MTS1/CDK41 gene show a greater tendency toward the development of recurrence and metastasis.