Faster Triage of Veterans With Head and Neck Cancer.

High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence.

BACKGROUND: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months. METHODS: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans. RESULTS: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive. CONCLUSIONS: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.

Nasopharyngeal carcinoma: salvage of local recurrence.

Local control of nasopharyngeal carcinoma has substantially improved with advancing radiotherapy technology and appropriate combination with chemotherapy. However, when local recurrence occurs, this is one of the most difficult challenges. Aggressive treatment is indicated because long term salvage is achievable particularly for early recurrence, but high risk of complications is a serious concern. Treatment options include different methods of surgery and/or re-irradiation with/without chemotherapy. Available information in the literature is grossly inadequate; most reports compose of small series of highly selected patients with heterogeneous characteristics and treatment. No randomized trials have been performed to evaluate the therapeutic ratio of different treatment methods. This article reviews available treatment options, their therapeutic benefits and risks of complications; the objective is to provide information for developing treatment recommendations and suggestions for future improvement.

Targeted endoscopic salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: Despite modern radiotherapy and open surgical techniques, treatment of recurrent nasopharyngeal carcinoma (NPC) remains challenging, with substantial morbidity involved. Targeted endoscopic nasopharyngectomy was evaluated as a viable oncologic alternative to open nasopharyngectomy or radiation for recurrent NPC. METHODS: Thirteen patients who underwent endoscopic nasopharyngectomy for recurrent NPC between August 2005 and August 2010 were retrospectively reviewed. Average age at surgery was 55.7 years, with mean follow-up period 24.2 months. Two-year disease-free survival, 2-year overall survival, margin status, and complication rate were measured. RESULTS: Including resections for subsequent recurrences, 19 endoscopic procedures were performed with curative intent. Mean operating room (OR) time was 278 minutes, mean estimated blood loss was 197 mL, and mean length of hospitalization was 1.0 days. Negative margins were obtained in 78.9% of procedures: positive margins involved the parapharyngeal space, oropharynx, fossa of Rosenmuller, and infratemporal fossa. Stereotactic radiation was given postoperatively for localized positive margins. Four patients required repeat endoscopic nasopharyngectomy for re-recurrence, despite having their margins cleared or controlled with adjuvant treatment. Two-year local disease-free and overall survival rates were 69.2% and 100.0%, respectively. The overall minor complication rate was 52.6%, with no major complications. CONCLUSION: Targeted endoscopic nasopharyngectomy is beneficial in locally recurrent NPC, with favorable morbidity and complication rates. Endoscopic surveillance and serial imaging together facilitate the early identification of re-recurrences, which often may be treated with additional directed resection. Postoperative stereotactic radiation may serve as an appropriate adjunct modality for disease control at positive margins.

A planned neck dissection is not necessary in all patients with N2-3 head-and-neck cancer after sequential chemoradiotherapy.

PURPOSE: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. METHODS AND MATERIALS: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. RESULTS: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). CONCLUSION: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer.

BACKGROUND: Cellular immune suppression is observed in head and neck squamous cell cancer (HNSCC) and contributes to poor prognosis. Restoration of immune homeostasis may require primary cell-derived cytokines at physiologic doses. An immunotherapy regimen containing a biologic, with multiple-active cytokine components, and administered with cytoxan, zinc, and indomethacin was developed to modulate cellular immunity. METHODS: Study methods were designed to determine the safety and efficacy of a 21-day neoadjuvant immunotherapy regimen in a phase 2 trial that enrolled 27 therapy-naïve patients with stage II to IVa HNSCC. Methods included safety, clinical and radiologic tumor response, disease-free survival (DFS), overall survival (OS), and tumor lymphocytic infiltrate (LI) data collection. RESULTS: Acute toxicity was minimal. Patients completed neoadjuvant treatment without surgical delay. By independent radiographic review, 83% had stable disease during treatment. OS was 92%, 73%, and 69% at 12, 24, and 36 months, respectively. Histologic analysis suggested correlation between survival and tumor LI. CONCLUSION: Immunotherapy regimen was tolerated. Survival results are encouraging.

Long-term great auricular nerve morbidity after sacrifice during parotidectomy.

OBJECTIVES/HYPOTHESIS: To clarify the extent and patient perspectives of great auricular nerve (GAN) morbidity and recovery after nerve sacrifice during parotidectomy 4 to 5 years after surgery. STUDY DESIGN: Prospective series. METHODS: Twenty-two patients who underwent parotidectomy with GAN sacrifice and were previously studied for GAN sensory outcome during the first postoperative year. We performed light touch sensation tests on each patient to develop an ink map representing anesthesia and paresthesia in the GAN sensory territory; patients also completed an outcomes questionnaire. RESULTS: Nineteen (86%) of 22 patients completed follow-up. One patient completed the questionnaire over the phone. The prevalence and average areas of anesthesia and paresthesia decreased since the first postoperative year according to sensory testing and patient scoring. At 4 to 5 years, 47% (9 of 19) of the patients had anesthesia, 58% (11 of 19) had paresthesia, and 26% (5 of 19) had neither anesthesia nor paresthesia during sensory testing. Patients reported that the GAN dysfunction brought them no to mild inference with their daily activities. At a mean point of 2 years, 70% (14 of 20) patients felt that their sensory symptoms had either completely abated or stabilized. CONCLUSIONS: The posterior branch of the GAN should be preserved if it does not compromise tumor resection. If this is not possible, the patient and surgeon should be comforted in that only minor, if any, long-term disability will ensue. Laryngoscope, 2009.

Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma.

PURPOSE: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. RESULTS: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. CONCLUSION: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

Quality of life 17 to 20 years after uvulopalatopharyngoplasty.

OBJECTIVES: To study the long-term quality of life outcomes of a group of unselected patients for the long-term effects of uvulopalatopharyngoplasty (UPPP). STUDY DESIGN: Retrospective chart review and telephone survey. METHODS: Forty-nine patients who underwent UPPP between July 1980 and July 1983 and who had their medical records were reviewed and were asked to grade on a visual analogue scale (VAS) the clinical benefits and complications of UPPP after the surgery. RESULTS: Forty-three (87.8%) males and six (12.2%) female patients were studied. Improvement in snoring, excessive daytime somnolence, and nocturnal arousals were seen after UPPP with decreased effectiveness after time. The most common complication of UPPP was velopharyngeal insufficiency (VPI) (28.5%); however, dry throat and swallowing difficulty tended to be more severe in those patients who had them. No correlation between the snoring and VPI VAS grades was observed. Forty-three patients had a preoperative sleep study and 22 patients a postoperative sleep study. There was lack of correlation between the significant subjective clinical improvement and their postoperative polysomnography. CONCLUSION: When undertaking UPPP, both subjective and objective benefits should be weighed against the risk of long-term ill effects. Patients should also be warned that the long-term side effects such as VPI, dry throat, and abnormal swallowing sensation might be more common than previously expected.

Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma.

BACKGROUND: Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT). METHODS: Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment. RESULTS: At a median follow-up of 25 months for living patients (range, 10-60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan-Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006). CONCLUSIONS: The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients.

Cyclin D1 and p16 expression in recurrent nasopharyngeal carcinoma.

BACKGROUND: Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. PATIENTS AND METHODS: A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. RESULTS: Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). CONCLUSION: While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated head and neck cancer, the level of p16 expression in recurrent NPC samples was much lower than that reported for previously untreated cancer. The finding that almost all (96%) of the recurrent NPC lack expression of p16 suggested that loss of p16 may confer a survival advantage by making cancer cells more resistant to conventional treatment with radiation +/- chemotherapy. Further research is warranted to investigate the clinical use of p16 both as a prognostic marker and as a potential therapeutic target.

Great auricular nerve morbidity after nerve sacrifice during parotidectomy.

OBJECTIVE: To clarify the extent, timing, and patient perspectives of great auricular nerve (GAN) morbidity and recovery after nerve sacrifice during parotidectomy during the first postoperative year. DESIGN: Prospective series. SETTING: Tertiary care academic medical center. Patients Twenty-seven consecutive patients who underwent parotidectomy with GAN sacrifice. MAIN OUTCOME MEASURES: Preoperatively and at 3, 6, 9, and 12 months postoperatively, we performed light touch sensation tests on each patient to develop an ink map representing anesthesia and paresthesia in the GAN sensory territory; patients also completed an outcomes questionnaire. RESULTS: Twenty-two (81%) of 27 patients completed follow-up. The prevalence and average area of anesthesia decreased continually during the first year according to sensory testing and patient scoring. Half of the patients had no anesthesia at 12 months. The prevalence and average area of paresthesia increased during the first year according to sensory testing; however, the contiguity and subjective scoring of paresthesia peaked at 6 months and decreased in subsequent follow-up points. Throughout the first year, patients had difficulty using the telephone, shaving, combing their hair, wearing earrings, and sleeping on the operative side because of both anesthesia and paresthesia. CONCLUSIONS: The impact of GAN sacrifice morbidity on patient quality of life is tolerable and improves during the first postoperative year. However, we feel that GAN morbidity may be bothersome enough to warrant efforts to preserve the posterior branch of the GAN when possible and appropriate.

Mature results from a randomized Phase II trial of cisplatin plus 5-fluorouracil and radiotherapy with or without tirapazamine in patients with resectable Stage IV head and neck squamous cell carcinomas.

BACKGROUND: The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC). METHODS: Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response. RESULTS: The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms. CONCLUSIONS: The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.

Advanced-staged tonsillar squamous carcinoma: organ preservation versus surgical management of the primary site.

BACKGROUND: Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site. METHODS: The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy. RESULTS: No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group. CONCLUSION: Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.

Positron-emission tomography for surveillance of head and neck cancer.

OBJECTIVES/HYPOTHESIS: To determine the diagnostic accuracy and the ideal timing of fluoro-fluorodeoxyglucose positron-emission tomography (PET) in the posttreatment surveillance of head and neck mucosal squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective chart review. METHODS: Our sample includes 103 adult patients with 118 posttreatment PET scans who had undergone treatment for HNSCC. We correlated PET results with surgical pathology and clinical outcome in the subsequent 6 months. RESULTS: For the detection of locoregional persistent or recurrent HNSCC, PET scans had a sensitivity of 82%, specificity of 92%, positive predictive value (PPV) of 64%, negative predictive value (NPV) of 97%, and overall accuracy of 90%. For the detection of distant metastases, PET scans had a sensitivity of 89%, specificity of 97%, PPV of 85%, NPV of 98%, and overall accuracy of 96%. PET scans of the head and neck region performed greater than 1 month after the completion of radiation compared with scans performed within 1 month had a significantly higher sensitivity of 95% versus 55% (P < .01) and NPV of 99% versus 90% (P < .01). CONCLUSION: PET is effective in detecting distant metastases in the posttreatment surveillance for HNSCC patients. A negative PET is highly reliable for all sites. However, a positive PET in the head and neck region is unreliable because of a high false-positivity rate. PET of the head and neck region has a statistically significant risk of a false-negative reading when performed within 1 month of radiation.

Split-thickness skin graft attachment to bone lacking periosteum.

OBJECTIVES: To develop an animal model to investigate the survival of split-thickness skin grafts (STSGs) on bone without periosteum, to compare STSG attachment to bone with and without periosteum, and to determine the effect of fibrin glue on STSG attachment to bone. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Sprague-Dawley rats. MAIN OUTCOME MEASURE: Percentage of survival of the STSGs at 2 weeks determined independently by the authors and a third, blinded head and neck surgeon. RESULTS: In experiment 1, which included 40 rats, the sutured STSGs showed an average survival rate of 38% when attached to bone with periosteum, 6% when attached to bare bone, and 10% when attached to bare bone using fibrin glue. The poor survival rate was thought to be attributable to the animals scratching at their bolster dressings. In experiment 2, 18 animals underwent a posteriorly based U-shaped flap of skin and subcutaneous tissue. The grafts were placed and isolated from the overlying flap with a biosynthetic wound dressing. The sutured STSG survival rates were as follows: 87% when attached to bone with periosteum, 94% when attached to bare bone, and 74% when attached to bare bone using fibrin glue. CONCLUSIONS: The survival of STSGs attached to bare bone was comparable to that of STSGs attached to bone with periosteum when grafts were protected with the skin-subcutaneous flap. The STSGs that were fixed with 0.1 cc of fibrin glue demonstrated poorer survival rates than those attached with sutures and were associated with more seromas.

Long-term results of 100 consecutive comprehensive neck dissections: implications for selective neck dissections.

OBJECTIVE: The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types. PATIENTS: The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence. RESULTS: Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%. CONCLUSION: Further study is needed to determine the optimal surgical management of the N0 and limited N+ neck.

Laryngeal embryonal rhabdomyosarcoma: a case of cervical metastases 13 years after treatment and a 25-year review of existing literature.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.

Identification of tyrosine kinases overexpressed in head and neck cancer.

OBJECTIVE: To identify protein-tyrosine kinases (PTKs) that may be involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). DESIGN: Messenger RNA from 7 HNSCC specimens was reverse transcribed to complementary DNA, and selective amplification of PTK complementary DNA was achieved using polymerase chain reaction (PCR) with degenerate PTK primers. The resulting PTK PCR products from these 7 HNSCC specimens were then cloned and randomly selected for sequencing. The PTKs that were represented multiple times in these randomly selected clones were selected as candidate PTKs that may be overexpressed in HNSCC. Antibodies against these candidate PTKs were then used for immunohistochemical studies on 8 other HNSCC specimens not used in the original selection of the candidate PTKs. RESULTS: Three known (EphA1, Brk, and Ron) and 2 novel (KIAA0728 and KIAA0279) PTKs were found to be highly expressed in the 7 HNSCC samples studied, based on the technique of reverse transcriptase-PCR with degenerate primers. Immunohistochemical studies with antibodies against the 3 known PTKs in 8 other HNSCC specimens not used in the previous reverse transcriptase-PCR reaction demonstrated overexpression of EphA1, Brk, and Ron in 12.5%, 37.5%, and 75% of these specimens. CONCLUSIONS: In this study, we identified 5 PTKs that were overexpressed in HNSCC using a reverse transcriptase-PCR technique and confirmed the overexpression of 3 known PTKs in some of the 8 archival HNSCC specimens studied. Our finding suggests that the signaling pathways mediated through EphA1, Brk, and Ron may be involved in the development and progression of HNSCC.