Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Neoadjuvant famitinib and camrelizumab, a new combined therapy allowing surgical resection of the primary site for anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid cancer (ATC) is considered the most lethal thyroid cancer, with an overall 5-year survival rate below 10%. The FDA approved a BRAF/MEK inhibitor combination for the treatment of patients with BRAF-mutated ATC. However, effective therapeutic options for patients with wild-type BRAF are lacking. CASE: In our phase II study, patients having advanced/metastatic solid ATCs were treated with famitinib and camrelizumab, a combination therapy involving a multi-targeted kinase inhibitor and an anti-PD-1 antibody. We report a case of a patient with locally advanced unresectable ATC who underwent this combination therapy, allowing us to perform complete surgical resection followed by post-operative radiation therapy. CONCLISION: To the best of our knowledge, this is the first report describing the use of famitinib and camrelizumab as a neoadjuvant treatment for ATC with wild-type BRAF. Clinical trial for a novel neoadjuvant approach for ATC are currently open for enrollment.

Integrated proteogenomic characterization of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.

Giant cell tumor in the thyroid area: a case report in the novel location and review of literature.

Giant cell tumor of soft tissue (GCT-ST) is a rare benign tumor of low malignant potential. It is thought to be the soft tissue counterpart of giant cell tumors of the bone due to its pathological resemblances. GCT-ST is most commonly found in superficial soft tissue of thigh, trunk and upper extremities. The head and neck region is rarely affected. Here for the first time, we describe a case of GCT-ST in the thyroid region. A 70-year-old female patient presented with a painless swelling in her left neck for the previous three weeks. The condition was initially diagnosed as thyroid goiter and left lobectomy was arranged. Intraoperative findings showed an irregular mass invading the strap muscles and trachea. Complete tumor resection was difficult, and part of the tumor was left in the thyroid bed. Histopathology of the resected specimen showed a mixture of mononuclear round to oval cells and multinucleated osteoclast-like giant cells. The giant cells were CD 68 positive. The patient received a revision surgery 3 months after the first operation to achieve complete resection. There was no recurrence in the first 3-month follow-up. However, 6 months after the revision surgery, the tumor recurred on both sides of the neck. The patient suffered from dysphagia and breathlessness. As further surgery and radiation therapy were not considered, denosumab was used as a novel agent After three months of treatment, the patient showed symptom-relief and tumor-regression. The patient continued to have tumor-regression after 1 year of the denosumab treatment. GCT-ST is a benign tumor, although in this case, it was showing features of malignancy. A review of the literature was conducted to identify previous studies on GCT-ST in the head and neck. We present this case for its rare location and novel treatment with denosumab.

Immune Co-inhibitory Receptors PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT in Medullary Thyroid Cancers: A Large Cohort Study.

CONTEXT: Programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to provide the first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTC patients. DESIGN AND PATIENTS: In total, 200 MTC patients who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMAs). Combined with the results of our previous programmed cell death ligand-1 (PD-L1) study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed. RESULTS: TIM-3, PD-1, CTLA-4, LAG-3, and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%), and 6 (3.0%) patients, respectively, in whom TIM-3, PD-1, and CTLA-4 expressions were positively correlated. Log-rank tests and multivariate Cox analyses both indicated that TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, among whom 6 cases also had concurrent moderate to strong PD-1, PD-L1, or CTLA-4 expression. CONCLUSIONS: Using the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for which single or combined immunotherapy including TIM-3, PD-1, PD-L1, or CTLA-4 blockade may be potential therapeutic approaches in the future.

Mammary analog secretory carcinoma of the thyroid gland: A rare cancer harboring TRK fusion.

Mammary analog secretory carcinoma (MASC), or secretory carcinoma of the thyroid is an extremely rare disease harboring ETV6-NTRK3 gene fusion with TRK activation. Here we report the twelfth case of MASC of the thyroid worldwide. A 36-year-old female was diagnosed with poor-differentiated thyroid carcinoma (PDTC). Pathology consultant and immunochemical workups showed the tumor cells were negative for TTF1, TG, PAX8, positive for S100, Vimentin, GATA-3, and focally positive for mammaglobin. Fluorescence in situ hybridization (FISH) assay using a dual-color break-apart probe showed ETV6 translocation t(12p13) (ETV6) was present and established the diagnosis of MASC. Next-generation sequencing (NGS) of a 47-gene panel identified exon 1-5 of ETV6 gene were fused with exons 15-19 of NTRK3 gene. The patient experienced three loco-regional recurrences within 12 months and eventually developed inoperable local disease as well as bilateral lung metastasis. She is currently receiving anti-TRK treatment with a follow-up time of 33 months. A literature review of MASC in the thyroid was also conducted.

Association Between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma.

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

Clinicopathological and Survival Outcomes of Well-Differentiated Thyroid Carcinoma Undergoing Dedifferentiation: A Retrospective Study from FUSCC.

BACKGROUND: Recently, several studies have reported that dedifferentiation occurs in fatal well-differentiated thyroid cancer (WDTC) cases. This study aimed at investigating the clinicopathological characteristics of WDTC undergoing dedifferentiation. METHODS: A total of 63 WDTC patients harboring dedifferentiated phenotype were enrolled in the study. The Kaplan-Meier method and Cox regression analysis were used to perform survival analyses. Harrell index of concordance (C-index) and Akaike information criterion (AIC) were calculated to compare the predictive value for prognosis among several prognostic classification systems. RESULTS: The median cause-specific survival (CSS) of patients was 138 months, with the CSS rate of 64.0% and 53.3% at 5 and 10 years, respectively. Presence of the anaplastic thyroid cancer (ATC) phenotype significantly increased the risk of poor CSS (P = 0.033), and age was the only independent risk factor for disease progression (P = 0.015). The C-index and AIC of the age, grade, extent, size (AGES) prognostic classification system for the CSS were 0.723 and 59.937, respectively. CONCLUSIONS: The presence of dedifferentiated phenotypes can be responsible for the poor outcomes in WDTC patients. The AGES system demonstrates to be an optimal prognostic system for WDTC undergoing dedifferentiation.

DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis.

DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/ß-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E-cadherin were found to be involved in the process. DIXDC1 enhanced ß-catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of ß-catenin in DIXDC1-overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E-cadherin and MMPs are also involved in this process. © 2015 Wiley Periodicals, Inc.

MRI and CT imaging characteristics of myoepithelioma of the parotid gland.

BACKGROUND: Myoepithelioma is a rare tumor of the salivary gland and only few reports have focused on its imaging characteristics. PURPOSE: To characterize the magnetic resonance imaging (MRI) and computed tomography (CT) characteristics of myoepithelioma of the parotid gland. MATERIAL AND METHODS: We retrospectively analyzed the MRI and CT findings of nine patients with myoepithelioma in the parotid gland as demonstrated by pathologic analysis. The MRI and CT findings were analyzed regarding the tumor position, size, marginal morphology, and degree and patterns of enhancement. RESULTS: Unilocular and multilocular tumors were found in seven cases (7/9, 77.8%) and two cases (2/9, 22.2%), respectively. Most of the tumors were located in the superficial lobe (6/9, 66.7%) and abutted the capsule of the parotid gland (7/9, 77.8%). Six of the seven unilocular tumors were round. Most of the tumors displayed smooth contours (6/9, 66.7%) and well-defined margins (5/9, 55.6%). Four of five tumors (80%) display the capsule on T2-weighted (T2W) and contrast-enhanced T1-weighted (T1W) imaging. All five examined tumors exhibited homogeneous intermediate signal intensity on T1W imaging and high signal intensity on T2W imaging. On contrast-enhanced T1W imaging, the tumors displayed homogeneous (n = 4) or heterogeneous (n = 1) moderate to marked contrast enhancement. Based on the enhanced CT scans, four tumors exhibited moderate homogeneous (n = 2) or heterogeneous (n = 2) contrast enhancement. CONCLUSION: Myoepitheliomas are characterized as small, unilocular, round tumors with smooth contours that are located in the superficial lobe and abut the capsule of the parotid gland, display the capsule on T2W and contrast-enhanced T1W imaging, and exhibit homogeneous signal intensities or densities based on MRI and CT.

A clinical analysis of 37 cases with lymphoepithelial carcinoma of the major salivary gland treated by surgical resection and postoperative radiotherapy: a single institution study.

The present study was undertaken to evaluate the diagnostic approaches, treatment results and failure patterns of lymphoepithelial carcinoma of the major salivary gland (LECSG). Patients were treated by definitive surgical resection and postoperative radiotherapy in an attempt to identify the proper strategies for the management of this disease. Patients with a histological diagnosis of primary lymphoepithelial carcinoma in the major salivary gland that was treated at our institution between January 2005 and December 2011 were comprehensively analyzed. An en bloc radical excision, which generally removes the salivary gland with level II and Ib lymph nodes, followed by postoperative radiotherapy was the standard treatment for this group of patients. Radical neck dissection was only performed in patients with metastatic lymphadenopathy. Postoperative irradiation was delivered to the tumor bed and involved nodes at a dose of 60 Gy and to the ipsilateral cervical lymph nodes at a dose of 56 Gy. Clinical and pathological factors correlated with locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) were analyzed using the log-rank test and a Cox proportional hazards model. A total of 37 patients with a median age of 45 years were enrolled in this study. The study population consisted of 21 males and 16 females. There were seven patients with stage I disease, 10 patients with stage II disease, nine patients with stage III disease and 11 patients with stage IV disease. With a median follow-up of 39 months (range 12-90 months), the 3-year LRC, PFS and OS were 94.3, 91.6, and 92.9%, respectively. Only two patients died of local-regional recurrences and distant metastases. No statistically significant prognostic predictors of LRC, PFS and OS were found. The presence of positive cervical lymph nodes showed a trend toward poorer outcome. Surgical resection with postoperative radiotherapy is a reasonable and proper treatment approach in the definitive management of LECSG and results in a favorable prognosis for a significant proportion of patients. No clinicopathological or therapeutic features were found to be suitable predictive factors for prognosis; thus, disease progression should be carefully monitored, especially for those patients with cervical node involvement.

Predictive index for lymph node management of major salivary gland cancer.

OBJECTIVES/HYPOTHESIS: To find the risk factors of lymph node (LN) metastasis of salivary gland cancer and draw a scheme for LN management. STUDY DESIGN: Hospital-based retrospective study. METHODS: The records of salivary gland cancer patients treated at the Department of Head and Neck Surgery, Cancer Hospital, Fudan University, were entered in a database, and 219 consecutive patients with carcinomas of major salivary glands primarily operated on between January 1998 and January 2011 were chosen for univariate and multivariate analysis to identify risk factors for LN involvement. RESULTS: Fifty-eight (26.5%) patients had LN involvement. Factors associated with cervical LN involvement on univariate analysis included pathologic type, male sex, shorter duration of preoperative course, facial paralysis, advanced T stage, and major nerve, soft tissue, lymphatic/vascular (L/V), neural/perineural, and extracapsular invasion. Multivariate analysis identified major nerve invasion, histologic type, L/V invasion, and extracapsular invasion as significant factors for LN involvement. The proportion of patients with LN involvement with low (105), middle (61), high (34), and super high (19) predictive index scores based on the four risk factors were 3.8%, 27.9%, 55.9%, and 94.7%, respectively. CONCLUSIONS: A predictive index using the clinicopathologic factors described in this report can effectively stratify patients into risk groups for nodal metastasis. Comprehensive management based on this risk index should improve treatment outcomes for patients with salivary gland cancer.

Clinicopathologic study of 1176 salivary gland tumors in a Chinese population: experience of one cancer center 1997-2007.

CONCLUSION: Chinese patients have a higher rate of lymphoepithelial carcinoma (LEC) and salivary duct carcinoma (SDC). Comprehensive use of diagnostic modalities, neck dissection, and postoperative radiation will improve the treatment results for salivary gland tumors (SGTs). OBJECTIVES: To study the clinicopathological characteristics of SGTs in a Chinese population. METHODS: The records of SGT patients operated in a tertiary cancer hospital of China were retrieved. RESULTS: From December 1997 to December 2007, 289 malignant and 887 benign SGTs were operated at Cancer Hospital, Shanghai, China. Pleomorphic adenoma and Warthin's tumor were the most common types of SGT. Mucoepidermoid carcinoma (24.6% of malignant cases) and adenoid cystic carcinoma (18.0%) were the most frequent malignant cases, followed by acinic cell carcinoma (12.1%), LEC (9.7%), and SDC (9.3%). The sensitivity and specificity of ultrasound scan, fine needle aspiration biopsy, and frozen section were 58.3 and 88.6%, 87.2 and 96.7%, 86.9 and 99.6%, respectively. Neck dissections and postoperative radiation were carried out for 48.6 and 48.0% of carcinomas, respectively. The percentage of tumors by pathologic TNM stage were 23.7% for stage I, 32.9% for stage II, 17.3% for stage III, and 26.1% for stage IV. The 5-year overall survival rate was 88.0%.

Gastrointestinal stromal tumor with structures resembling intracytoplasmic lumina.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gut. It is characterized by positive immunostaining for CD117, and bears mutations in the c-kit or PDGFRA genes. Its origin remains uncertain. GISTs mainly possess primitive smooth muscle or neuronal differentiation. Although an epithelioid pattern of GIST is a common finding on light microscopy, true epithelial differentiation has never been demonstrated by either immunohistochemistry or ultrastructural study. Here the authors report an epithelioid GIST of the stomach, immunopositive for CD117, DOG1.1, CD34, and PDGFRA, with slight cytoplasmic staining for epithelial membrane antigen. One heterozygous mutation on codon 842 of exon 18 of the PDGFRA gene was also found. Ultrastructurally, tumor cells had plentiful organelles, including some membrane-bound, dense-core granules and cytoplasmic vacuoles. Intermingled thin cellular processes were also found. Unusually, there were many structures resembling glandular epithelial intracellular lumina with processes. The processes, although resembling microvilli, did not have filament cores, while the lumina were either empty or contained some dense or flocculent content of uncertain nature. True intracellular lumina are very rare in GIST and the authors present findings related to this issue, with a discussion on their nature, origin, and significance.

14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition.

ErbB2, a metastasis-promoting oncoprotein, is overexpressed in approximately 25% of invasive/metastatic breast cancers, but in 50%-60% of noninvasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3zeta in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3zeta overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3zeta overexpression reduced cell adhesion by activating the TGF-beta/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition. Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3zeta had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.

Case report of extrarenal rhabdoid tumor of pelvic retroperitoneum molecular profile of angiogenesis and its implication in new treatment strategy.

We report the detailed molecular study of angiogenesis-ralated genes and target therapy of the case of a male 46-year-old patient with extrarenal rhabdoid tumor of pelvic retroperitoneum. The patient was found to have a huge pelvic soft tissue sarcoma and underwent pelvic tumorectomy and appendectomy. The microscopically morphological features and molecular profile by immunohistochemical analysis supported the surgical histological diagnosis of extrarenal rhabdoid tumor. The tumor recurred two weeks after surgery and metastasized to the lung, left abdominal wall and mesenteric lymph nodes. Systemic chemotherapy including ifosfamide, liposomal doxorubicin, Taxol and cisplatin, concurrently with pelvic radiotherapy (58 Gy of total dose). However, the patient did not respond to the combination of chemotherapy and radiotherapy. Immunohistochemical staining and fluorescence in situ hybridization of tumor cells indicated negative expression of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) and positive expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). So anti-VEGF targeted therapy (Bevacizumab) was administered following the fourth course chemotherapy. However, the condition worsened after the administration of the second cycle of Bevacizumab. Multiple organ failure led to the death of the patient. The patient only survived five months and 20 days after the surgery of the primary tumor.

[Thirty base pair (30 bp) deletion in latent membrane protein 1 oncogene in lymphoepithelial carcinoma of salivary glands].

OBJECTIVE: To investigate 30 bp deletion of latent membrane protein (LMP)-1 gene in lymphoepithelial carcinoma (LEC) of the salivary glands and to determine the frequency of this deletion. METHODS: Forty-six cases of salivary gland LEC were investigated by PCR to explore the site specific, 30 bp deletion in the 3' terminal region of LMP-1 gene. To guarantee amplifiable DNA extracted from paraffin-embedded tissue sections, PCR amplification of a house-keeping gene (beta-actin) was performed simultaneously. In addition, DNA sequencing of the PCR product was performed in representative cases. RESULTS: Although amplifiable DNA was obtained in 42 of the 46 specimens, as indicated by beta-actin gene amplification, successful amplification of LMP-1 gene was achieved in 35/42 (83.3%) cases. Two types of PCR products of LMP-1 gene were observed and confirmed by DNA sequencing. A wild-type PCR product (316 bp) was present in 31 cases (88.6%) and only 4 cases (11.4%) showed an aberrant 286 bp PCR product, corresponding to the 3' terminal 30 bp deletion of the gene. CONCLUSION: Site-specific 30 bp deletion of LMP-1 gene is not a common feature of salivary gland LEC.