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Postoperative adjuvant therapy has been indicated by advanced T classification for T3–4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3–4 OSCC remains unclear. Ninety-eight cumulative patients with T3–4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p p = 0.017, and p

Perineural invasion (PNI) has been an established poor prognostic feature for T1-T2 oral squamous cell carcinoma (OSCC). Different presentations and amounts of PNI are commonly observed, but PNI is currently recorded as being present or absent. This study asked whether the quantification of PNI provides additional information for early OSCC.Retrospective cohort study.Tertiary referral medical center.Pathologic reevaluations were performed for 314 patients with T1-T2 OSCC who underwent curative surgery from June 2001 to August 2009. A novel parameter, PNI focus number, was defined for PNI quantification. With 5 PNI foci as the cutoff, patients were categorized into 3 groups: no PNI (0 PNI foci), low PNI (PNI foci, 1-5), and high PNI (PNI foci5). Rate of cervical lymph node metastasis (LN+), 5-year disease-specific survival (DSS), and 5-year overall survival (OS) were analyzed among these groups.PNI focus number independently predicted for LN+, poor DSS, and poor OS in multivariate analysis after controlling for T classification, lymphovascular invasion, differentiation, margin, and tumor thickness. The 5-year DSS demonstrated a dose-dependent decrease among the 3 groups (no PNI, 88.6%; low PNI, 75.2%; high PNI, 33.8%; P.001). Moreover, the 5-year DSS of the high PNI group was significantly worse than that of the low PNI group.PNI focus number can be a novel parameter for PNI quantification in early OSCC. Although optimal quantification methods still require further investigation, this study offers clear clinical support for the nerve-tumor interaction hypothesis and advocates further mechanistic research for the exploration of PNI-related treatment concepts for OSCC.

Aims Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a newly described entity of the sinonasal tract. In this study, we evaluated histomorphology, immunophenotype and molecular testing to identify potentially helpful features in distinguishing it from classic adenoid cystic carcinoma (AdCC). Methods and results We retrospectively collected five HPV-related carcinomas with adenoid cystic-like features and 14 AdCCs of the sinonasal tract. All histological slides were retrieved for morphological evaluation. As comparing with AdCC, HPV-related carcinomas with adenoid cystic-like features were associated with squamous dysplasia of surface epithelium (80% versus 0%, P < 0.01) and the presence of a solid growth pattern (100% versus 29%, P = 0.01), but less densely hyalinized tumour stroma (20% versus 86%, P = 0.02). Squamous differentiation in the invasive tumour was seen in three HPV-related carcinomas with adenoid cystic-like features, two of them showing abrupt keratinization and one with scattered non-keratinizing squamous nests. Diffuse p16 staining in ≥75% of tumour cells was noted in all HPV-related carcinomas with adenoid cystic-like features but in only one AdCC (100% versus 7%, P < 0.01). High-risk HPV testing gave positive results in all HPV-related carcinomas with adenoid cystic-like features (four associated with type 33 and one associated with type 16) but not in AdCCs. MYB rearrangement was tested in four HPV-related carcinomas with adenoid cystic-like features, and all were negative. Conclusions This study has further clarified the histological spectrum of this tumour type, and reports the first HPV type 16-related case. Diffuse p16 staining followed by HPV molecular testing is useful in distinguishing HPV-related carcinomas with adenoid cystic features from classic AdCCs.

To investigate the clinicopathologic characteristics of patients with immunoglobulin G4-related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease.Case series with chart review and pathology study.Tertiary care hospital.We evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared.Of the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P.001). Ratio of IgG4-positive plasma cells to IgG-positive plasma cells in IgG4-RCSS tissues was 0.81 ± 0.14. The mean value of serum IgG4 in IgG4-RCSS patients was 918.8 mg/dL.IgG4-RCSS is more common in older male patients and frequently presents with bilateral involvement. Informing head and neck surgeons of the clinical features of IgG4-RCSS and promoting a combined approach of clinical evaluation, imaging, and biopsy can improve the accuracy of preoperative diagnoses.

Cell surface proteins such as CD44 and CD24 are used to distinguish cancer stem cells (CSCs) from the bulk-tumor population. However, the molecular functionalities of CD24 and CD44, and how these two molecules coordinate in CSCs remain poorly understood. We found that nasopharyngeal carcinoma (NPC) cells with high expression of CD44 and CD24 proteins presented with pronounced CSC properties. Accordingly, a subpopulation of NPC cells with co-expression of CD44 and CD24 were specially enriched in high-stage clinical samples. Furthermore, ectopically expressing the epithelial-mesenchymal transition (EMT) regulator Twist was able to upregulate the stemness factors, and vice versa. This indicates a reciprocal regulation of stemness and EMT. Intriguingly, we found that this reciprocal regulation was differentially orchestrated by CD44 and CD24, and only simultaneous silencing the expression of CD44 and CD24 led to a broad-spectrum suppression of CSC properties. Oppositely, overexpression of CD44 and CD24 induced the reprogramming of parental NPC cells into CSCs through STAT3 activation, which could be blunted by STAT3 inhibition, indicating that CD44 and CD24 collaboratively drive the reprogramming of NPC cells through STAT3-mediated stemness and EMT activation. Consequently, targeting of the CD44/CD24/STAT3 axis may provide a potential therapeutic paradigm for the treatment of NPC through repressing CSC activities.

Summary Carcinoma cuniculatum, also known as cutaneous verrucous carcinoma, is a rare, low-grade, well-differentiated squamous cell carcinoma usually involving the foot. It is often locally aggressive but rarely metastatic. Only 10 cases involving the skin of the face (except the lips and scalp) have been reported. We describe a 74-year-old man who presented with carcinoma cuniculatum on the nasal tip arising from a keratoacanthoma-like lesion. To our knowledge, this is the first report of such a case in the literature. Literature related to carcinoma cuniculatum is also reviewed, and the challenges in diagnosis and choice of treatment are also described. In this case, the patient initially presented with keratoacanthoma on the nasal tip, and rapid recurrence with a verrucous mass occurred 1 month following tumor excision. Wide excision with 5-mm safe margins and full-thickness skin graft resurfacing were performed smoothly after recurrence. Histopathologic examination revealed carcinoma cuniculatum. The patient recovered uneventfully, and no recurrence of the lesion was reported over a 62-month period of observation. Overall, the prognosis of carcinoma cuniculatum is usually favorable. However, early diagnosis and treatment of carcinoma cuniculatum are crucial by clinicopathological standards. General clinical awareness of this entity contributed to more appropriate and timely treatment.

Objectives Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve-tumour interactions have been implicated for its pathogenesis. Design and setting Systematic investigation of nerve-tumour interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human peripheral nerves to enhance OSCC migration/invasion. Retrospective cohort study was also carried out in one medical centre from 2001 to 2009. Participants 314 T1-2 OSCC patients. Main outcome measures In the transwell migration/invasion assay, the cells in five representative fields were counted. In the nerve implantation model, tumour size was estimated. PNI quantification by PNI focus number was carried out in the OSCC patients to correlate with cervical lymph node metastasis and oncologic outcomes. Results The transwell migration/invasion assay demonstrated that human peripheral nerves, compared with subcutaneous soft tissue, significantly enhanced the migration/invasion abilities of OSCC. Moreover, the enhanced migration was dose-dependent with increased length or number of peripheral nerve segments. The nerve implantation model showed that human peripheral nerve also enhanced OSCC growth in vivo. Finally, increased PNI focus number was found dose-dependently associated with increased cervical lymph node metastasis and decreased 5-year disease-specific survival rates. Conclusions These results clearly indicated the presence of nerve-tumour interaction that involved paracrine influences leading to aggressiveness of OSCC. Further investigations are required to explore key cell types and molecules involved in nerve-tumour interactions for future therapeutic targeting of PNI in OSCC.

Ludwig's angina is a life-threatening cellulitis that involves the submandibular and sublingual spaces. It often occurs after an infection of the roots of the teeth. However, modern dental care and use of antibiotics for oral infections have made Ludwig's angina rare. We present here a cancer patient exhibiting the sequential features of bisphosphonate related osteonecrosis of the jaw on bone scan complicating with Ludwig's angina. This report highlights the need for medical practitioners to be alert to these rare combinations in the compromised patient after bisphosphonate therapy. To the best of our knowledge, no case of Ludwig's angina secondary to osteonecrosis of the jaw has been reported.

Acute pharyngitis is a common disease. However, acute pharyngitis caused by Klebsiella pneumoniae with a gross appearance mimicking hypopharyngeal malignancy has never previously been reported. We report the case of a 57-year-old man with a right hypopharyngeal tumor which was disclosed by fiberoptic laryngoscopy and computed tomography scan. However, both the frozen and final pathologies showed no evidence of malignant cells, and a bacterial culture revealed the growth of K. pneumoniae. The hypopharyngeal lesion completely regressed after 2 weeks of antibiotic treatment. Clinicians should perform biopsy along with tissue culture for tumor-like lesions because infectious agents can lead to lesions with malignancy-like appearance.

// Yi-Fen Wang 1,2 , Chun-Ju Chang 3 , Jen-Hwey Chiu 4 , Chin-Ping Lin 5 , Wing-Yin Li 2,6 , Shyue-Yih Chang 1 , Pen-Yuan Chu 1,2 , Shyh-Kuan Tai 1,2 , Yu-Jen Chen 4,5,7 1 Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2 Department of Medicine, National Yang Ming University, Taipei, Taiwan 3 Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan 4 Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan 5 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 6 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan Correspondence: Chun-Ju Chang, email: // Yu-Jen Chen,, email: // Keywords : Head and neck squamous cell carcinoma (HNSCC); NM23-H1; Metastasis; Cisplatin; Prognosis Received : February 20, 2014 Accepted : April 16, 2014 Published : April 18, 2014 Abstract We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients’ prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.

Tympanomastoid surgery constitutes the vast majority of procedures performed by otologists. Intra-operatively, identifying the facial nerve is always a challenge. We present an unusual case of fibrous connective tissue mimicking a facial nerve variant during cholesteatoma surgery. The variant was inadvertently damaged during surgery, and we feared devastating complications; however, the pathology revealed that it was not the actual facial nerve. This case is important, in that it serves as a reminder for otologists to be aware of the many possible presentations of the facial nerve in otologic surgery.

Observation or elective neck dissection (END) for cN0 neck remains controversial for the treatment of T1-2 oral squamous cell carcinoma (OSCC). Perineural invasion (PNI) has been recognized as a poor prognostic factor for OSCC. However, its significance in T1 OSCC remains unclear. A detailed histologic reevaluation of PNI was carried out in 307 patients with T1-2 OSCC who received surgical treatment between June 2001 and January 2009. We found that the presence of PNI correlated with cervical lymph node metastasis in both T1 and T2 OSCC, with a lower PNI-positive rate in T1 (17.1% vs. 36.6%; P

Neck management for cN0 neck remains controversial for T1-2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear.Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1-2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed.Increased tumor thickness (6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI.PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1-2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.

Objectives Perineural invasion (PNI) is an established poor prognostic pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this study was to analyze the role of pretreatment parameters in predicting PNI for OSCC. Materials and methods We prospectively enrolled into our study 102 newly diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before treatment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue scale (VAS) for cancer pain. Pathological examination was performed to ascertain PNI status in all patients. Patients were divided into two groups, those with PNI and without PNI. Pretreatment parameters were compared between the two groups. Results In univariate analysis, clinical T classification ( P P = 0.001), problem with social eating ( P P = 0.002), VAS scores of primary pain ( P P = 0.004) were found to be associated with PNI. Multivariate logistic regression analysis further revealed VAS score of primary pain ( P = 0.001, OR 2.014) and T3-4 classification ( P = 0.014, OR 6.422) were independent predictors of PNI. A regression equation incorporating pretreatment pain was developed to predict the probability of having PNI. Conclusion PNI can be predicted by higher pretreatment VAS score of primary pain, as well as more advanced clinical T classification. Careful evaluation of pretreatment pain of primary tumor can thus be helpful in improving treatment decision making for OSCC.

Background. Recent studies have indicated hedgehog pathway plays a role in carcinogenesis of certain cancers. We investigated the clinical significance of its signal- ing components, including Sonic hedgehog (Shh), Patched (Ptch), and Gli-1, in oral squamous cell carcinoma (OSCC). Methods. By immunohistochemistry, we determined Shh, Ptch, and Gli-1 expression in surgical specimens from 40 patients with OSCC. The relationship between expression of these molecules and clinicopathologic variables were assessed by chi-square analysis. Statistical difference of sur- vival was compared using log-rank test. Results. Ptch overexpression was associated with lym- phatic metastasis (p ¼ .028). Nuclear Gli-1 overexpression cor- related with primary tumor size (p ¼ .001), lymphatic metastasis (p ¼ .011), and tumor recurrence (p ¼ .008). Over- expression of Ptch (p ¼ .020) or Gli-1 (p ¼ .002) in OSCC indi- cated poor prognosis in the univariate survival analysis. Conclusion. Our results suggest sonic hedgehog (Shh) pathway plays an important role in OSCC progression and should be considered a potential therapeutic target. V C 2012 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2012

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.

Metastatic colon cancers to the oral cavity are unusual, involving a majority of the mandible rather than the oral soft tissues. We describe a rare site of gingival metastasis in a case of rectosigmoid cancer. The patient was a 74-year-old woman who developed swelling and persistent bleeding of the right mandibular gingiva after tooth extraction. A PET/CT using 18F-FDG depicted multiple metastatic lesions in the neck, lung, abdominal wall, and mandibular gingiva. Histologic study of the gingival lesion confirmed the diagnosis of gingival metastasis from colon adenocarcinoma.

The function of EZH2 in tumorigenesis and liver metastasis of pancreatic cancer has never been elucidated in vivo. EZH2 was overexpressed in pancreatic carcinomas and its overexpression was associated with tumor differentiation and pT status. Suppression of EZH2 caused a significant growth inhibition of pancreatic cancer cells in vitro and markedly diminished their tumorigenicity in vivo. Knock-down of EZH2 inhibited liver metastasis of pancreatic cancer in vivo. EZH2 has a crucial role in tumor growth and liver metastasis of pancreatic cancer.

A mass in the nasopharynx often implies a malignancy in adults, particularly in the endemic areas of Epstein-Barr virus-associated undifferentiated carcinoma. We report an 86-year-old male patient who presented to our rhinologic outpatient department with postnasal drip for several years, with no other associated nasal symptoms. Physical examination with nasal endoscopy found a prominent bulge in the nasopharynx. Pathological examination of the biopsied specimens identified features consistent with amyloidosis. Magnetic resonance imaging demonstrated an enhanced soft-tissue mass localized to the nasopharyngeal region. We excluded the possibility of a partial representation of a potential systemic amyloidosis. Regular follow-up including nasal endoscopy was undertaken. Over 3 years of observation, the disease process remained silent. Here, the clinical presentation, diagnosis and treatment options of this rare entity are discussed.

Rationale:Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and revi

Oncocytic carcinomas of the nasal cavity are extremely rare. We report 1 patient whose primary tumor and neck lymphadenopathies were under control nearly 2 years after combined surgery and radiotherapy. An 80-year-old man with a history of nasal oncocytoma had received excision twice previously. Computed tomography demonstrated locally advanced recurrent tumor invading the paranasal sinuses and orbit with lymphadenopathies in the right neck. Skull base surgery was performed. Pathological examination revealed oncocytic carcinoma. Positron emission tomography showed hypermetabolic lesions in the surgical bed and right neck. The patient subsequently received intensity-modulated radiotherapy to the primary site and the whole neck. Follow-up computed tomography 4 months later showed marked shrinkage of the neck lymphadenopathies. There was no progression after nearly 2 years. Although these tumors have historically been regarded as radioresistant, the combined treatment of surgery followed by radiotherapy may offer the best chance for control of locally advanced disease.

Primary malignant melanoma rarely occurs in the external auditory canal. In the few reported cases, treatment with lateral temporal bone resection, superficial parotidectomy, and neck dissection were suggested. We describe a 52-year-old man with this disease, managed by sentinel node biopsy with lymphoscintigraphy guidance, lateral temporal bone resection, and postoperative radiotherapy. The patient refused superficial parotidectomy and neck dissection. Although there was no locoregional recurrence on follow-up, pulmonary metastasis was diagnosed in the third year after treatment. The incidence, symptoms, treatment, and prognosis of external auditory canal malignant melanoma are also discussed in this article.

Patients with sino-nasal neuro-endocrine carcinoma should be managed by multi-modality treatment that includes surgery and postoperative chemo-radiotherapy as described in our treatment plan. Even though current combined therapy results in good disease control and survival rate, long-term follow-up is necessary.Neuro-endocrine carcinoma is an aggressive and rare malignant tumor of the sino-nasal tract, and its management remains divergent. The aim of this paper is to present our experience in the management of this kind of aggressive tumor and compare different treatment plans in order to draw up an effective strategy. Various treatment strategies were reviewed and assessed.Seven patients with biopsy-proven primary sino-nasal neuro-endocrine carcinoma from July 2004 to December 2006 were evaluated. The staging system was based on the American Joint Committee on Cancer Staging Manual of 2002. All of the patients underwent endoscopic or open surgery with curative intent. Six patients received postoperative chemo-radiotherapy.The median follow-up after surgery was 43.5 months (range 26.9-57.7 months). One patient was T2N0M0, one was T3N0M0, four were T4aN0M0, and one was T4bN0M0. After endoscopic or open surgery and postoperative chemo-radiotherapy, six patients were alive with no evidence of recurrence. One patient had persistent tumor without clinical and imaging changes for 36.9 months. After the whole treatment course, one patient had sino-cutaneous fistula and underwent flap reconstruction. None had regional failure or distant metastasis during follow-up.

A series of 76 cases of gastrointestinal tract endocrine tumors, including 21 poorly differentiated endocrine carcinomas (PDECs, small cell carcinomas) and 55 well-differentiated endocrine neoplasms (WDENs, carcinoids), 18 metastatic and 37 nonmetastatic rectal carcinoids, were examined by immunohistochemical analysis for p16INK4a, cyclin D1, and retinoblastoma protein (pRB) expression. Overexpression of p16INK4a was noted in 16 (76%) of the PDECs and none of the WDENs (P < .0001). Loss of pRB expression was demonstrated in 14 (67%) of the PDECs and 17 (31%) of the WDENs (P = .004). Overexpression of cyclin D1 was noted in 49 (89%) of the WDENs and 3 (14%) of the PDECs (P < .0001). Loss of pRB expression was noted in 11 (61%) of 18 metastatic WDENs and only 6 (16%) of 37 nonmetastatic WDENs (P = .001). The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors, and the loss of expression of pRB may be helpful in identifying patients at high risk of metastasis in rectal WDENs.

The overall prognosis for tongue cancer patients in Taiwan is unpredictable, even when patients are treated following the guidelines according to TNM stages. In order to determine the optimal treatment modality for tongue cancer in Taiwan the authors aimed to correlate histopathological parameters with neck nodal metastasis. A retrospective analysis of 94 patients with different stages of tongue cancer treated in the Taipei Veterans General Hospital was performed. All 94 patients were clinically diagnosed with stage I-IV tongue cancer before surgery and received primary tumor-wide excision and neck dissection. There were 42 (45%) patients with nodal metastasis. Univariate analysis revealed that cases of tongue cancer with moderate or poor differentiation, an invasion depth more than 3 mm and positive perineural invasion or lymphovascular permeation at the time of presentation may be subject to a higher incidence of neck nodal metastasis. An elective neck dissection or neck treatment should be considered if these histopathological risk factors are present. Cases of tongue cancer with these risk factors also warrant close follow-up after surgery.

Cervical cysts are usually benign in the population younger than 40 years. However, neck metastasis from malignancies of the head and neck may present as cervical cysts. Here, we report a case of papillary thyroid carcinoma with cervical metastasis and cystic change. A 35-year-old man visited our clinic, and his chief complaint was related to the presence of a huge neck mass for 15 years. Computed tomography scans revealed cystic masses and abnormal calcification in the thyroid gland. Fine needle aspiration cytology of the left thyroid gland revealed atypical cells with a few cells harboring intranuclear pseudoinclusion. We then performed dissection of the left side of the neck to remove the cystic masses and a left thyroid lobectomy. Intraoperative frozen section biopsy of the cystic masses showed benign cystic lesions. However, the results of the final pathologic examination proved thyroid papillary carcinoma in the thyroid gland and the cystic masses. The patient received dissection of the right side of the neck accompanied by right thyroid lobectomy. After the operation, 131I ablation therapy was performed. There was no recurrence noted during the regular 2-year follow-up period.

Objectives: Hypopharyngeal squamous cell carcinoma (HPSCC) usually presents at an advanced stage. Although chemo-radiotherapy has become more popular in treating HPSCC in recent years, surgery with postoperative adjuvant therapy still plays an important role. The purpose of this study was to identify the clinicopathologic factors that predict survival in patients with HPSCC who underwent surgical treatment. Methods: Between 1986 and 1995, 94 previously untreated HPSCC patients who underwent surgery with or without postoperative radiotherapy were enrolled. The surgical specimens were reexamined by a single pathologist. The clinicopathologic parameters and prognostic data were analyzed. Results: With a median follow-up of 50 months, the 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were 47%, 60%, and 58%, respectively. Thirty-seven patients (39%) had tumor recurrence. The level of lymph node metastasis was an independent factor in OS, DSS, and RFS. Neck biopsy before surgery, tumor involvement of more than 1 subsite, and extracapsular spread were independent factors in DSS, as was lymphovascular permeation in RFS. Conclusions: The level of cervical lymph node metastasis is the only independent prognostic factor in OS, DSS, and RFS. The addition of postoperative chemoradiotherapy may benefit high-risk cases.

OBJECTIVE. Basal cell adenoma is a rare benign epithelial tumor of the salivary gland. The objective of this study is to present the CT findings of parotid basal cell adenoma. We also compare CT findings of basal cell adenoma with those of pleomorphic adenoma, the most common parotid tumor, to determine whether any features on CT can help differentiate these two entities.CONCLUSION. Basal cell adenomas of the parotid gland are located chiefly in the superficial lobe. They are generally round, well-circumscribed tumors that show heterogeneous enhancement on CT. The age of the patient and the attenuation on unenhanced and contrast-enhanced CT may help in differentiating basal cell adenoma from pleomorphic adenoma of the parotid gland.

We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens.

Awoman in her 50s presented with a several-month history of symptoms that included foreign body sensation in her throat, mild odynophagia, and dyspnea. She had a history of adenoid cystic carcinoma of the right submandibular gland and had undergone wide tumor excision and postoperative radiation therapy 20 years previously (60Gy/30 fractions in 1993). She also had a history of hyperthyroidism,whichwas undermedical control (with propylthiouracil, 50mg/d). She stated that she did not have blurred vision, headache, seizures, or trismus. She had no family history of neurofibromatosis. A physical examination revealed a bulge in the floor of mouth, limitation of tongue movement, and no palpable lymphadenopathy. Shehadnosuspicious spotsornoduleson theskin.Noneurological deficits were revealed. Postgadolinium T1-weighted magnetic resonance imaging disclosed a 7.0 × 4.0 × 3.0-cm,well-definedenhancingmass in the right sideof the floorof themouth, extending posteriorly to the tongue base andmedially across the midline (Figure, A). The results of laboratory investigations were normal. Transcervical removal of the tumor was performed. The surgical specimen was a 7.2 × 5.8 × 4.3-cm encapsulated tumor composed of a homogeneous, whitish, rubbery, and glistening content (Figure, B). Microscopic examination demonstrated oval to eel-like spindle nuclei distributed in a backgroundofgenerallywavycollagenous fibers andmucinousmatrix (Figure,C). Thespecimen showed sparse cellularity and no cellular atypia. Neither mitotic figure nor tumor necrosis wasfound.Thespecimenwas immunoreactive forS-100(Figure,D), focallypositive forCD34, but nonreactive for smoothmuscle actin. A B

BackgroundSalivary gland carcinomas of the larynx are rare, and account for

Background Sarcomas of the larynx are rare neoplasms that constitute less than 1% of laryngeal malignancies. A Medline search found no large series focusing on laryngeal sarcomas. We reviewed the cases of laryngeal sarcomas treated in our cancer center and compared our experiences and treatment results with those from other centers. Methods A retrospective review of 10 patients with laryngeal sarcoma treated in our institute between 1980 and 2000 was done to identify tumor characteristics, therapeutic modalities, and treatment outcomes. Results The patients showed a male predominance (9/10) and presented 8 types of pathology. Nine patients underwent surgery, including 2 total laryngectomy, 4 partial laryngectomy, and 3 endoscopic laser cordectomy. During a median follow-up of 92 months, the 5-year overall survival and disease-specific survival were 76% and 90%, respectively. Two patients developed recurrence, including 1 local recurrence and 1 distant metastasis. Conclusion Surgical intervention was the first choice in the treatment of laryngeal sarcomas. The prognosis is relatively good when compared with sarcoma originating from other anatomic sites.

Purpose and Experimental Design: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non–small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme–based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. Results: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). Conclusion: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.

Chronic sclerosing sialadenitis (CSS), or Kuttner tumor, is a benign inflammatory process of the major salivary gland that occurs almost exclusively in the submandibular gland of middle-aged adults. It is rarely reported to involve the parotid gland or to occur in adolescents. 1 Chronic sclerosing sialadenitis is characterized histologically by periductal fibrosis, dense lymphocytic infiltration with lymphoid follicle formation, loss of the acini, and, eventually, marked sclerosis of the salivary gland. 2 , 3 This lesion has been recognized as a distinct clinicopathologic entity in the latest edition of the World Health Organization classification of tumorlike lesions of the salivary glands. 2 Because CSS manifests as a hard mass, it usually raises a strong clinical suspicion of a malignant neoplasm. In recent years, gray scale sonography and color Doppler sonography (CDS) have been widely used in the evaluation of major salivary gland masses, and fine-needle aspiration cytologic examination and needle biopsy have been used increasingly as cost-effective and safe techniques to confirm or evaluate salivary gland lesions.4-6 We report the sonographic and CDS manifestations and sonographically guided needle biopsy histologic features of an adolescent with CSS of the unilateral parotid gland.

Objectives: Tumor recurrence and metastasis are major causes of treatment failure in esophageal squamous cell carcinoma (ESCC). Recently, nm23, originally considered to be an anti-metastatic gene, has been reported to associate with various roles in different human cancers. We therefore investigated the clinical significance of nm23-H1 expression in ESCC. Methods: Pathological sections were immunohistochemically stained with monoclonal antibody that was specific to nm23-H1. Expression of positive nm23-H1 staining was further confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between nm23-H1 expression and clinicopathological variables was examined by statistical analysis. Except for 11 (7%) surgical morality, the remaining 145 patients entered the prognostic analysis. The cisplatin-based chemotherapy was established for the patients with tumor stages at or beyond IIb, or with tumor recurrence. Survival difference between groups was compared by log rank test. Results: Immunohistochemically, nm23-H1 expression was detected in 39.3% (57/145) of the pathological sections. It was positively correlated with tumor stage ðP ¼ 0:002Þ; evident lymphovascular invasion ðP , 0:001Þ and tumor recurrence ðP ¼ 0:02Þ: Survival of nm23-H1 positive group was statistically superior to nm23-H1 negative group ðP , 0:0001Þ: By multivariate survival analysis, tumor stage, the number of lymph node metastasis and expression of nm23-H1 were the independent prognostic factors for ESCC patients. Conclusions: Our study demonstrated that nm23-H1 expression was associated with disease progression in ESCC. However, survival of nm23-H1 positive group was superior to nm23-H1 negative group. This paradoxical result could suppose that nm23-H1 expression might increase cisplatin chemosensitivity and hence improve survival. Screening for nm23-H1 expression in tumor cells may be a potential therapeutic strategy in ESCC patients. q 2004 Elsevier B.V. All rights reserved.

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.

We present a rare case of oral metastatic epithelioid sarcoma rapidly growing over the mandibular gingivae; the primary lesion occurred on the wrist and was treated 18 months earlier by surgery and radiotherapy. The oral metastatic lesion was resected and controlled by chemotherapy. This case has been followed for 2 years with good control of the resected oral metastatic lesion. Histologically, round to oval-shaped tumour cells with abundant eosinophylic globular cytoplasm and eccentrically localized nuclei, lack of epithelial features by electron microscopic study, and the immunohistochemical and cytologic features of tumour cells led into the diagnosis of epithelioid sarcoma. To our knowledge, no reports have been published of its occurrence in the oral cavity

We investigated the significances of the expressions of dihydrodiol dehydrogenase (DDH) and glutathione-S-transferase (GST) in patients with esophageal squamous cell carcinoma (ESCC). By using immunohistochemistry, we measured expressions of DDH, GST, COX-2, nm23-H1, HER-2/ neu and mdr-1 in 145 patients with ESCC. Expression of DDH was confirmed by immunoblotting and reverse transcription-polymerase chain reaction. Relation between DDH expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log rank test. DDH overexpression was detected in 66.9% of pathological sections (97/ 145) and in 41.6% of metastatic lymph nodes (37/89). The nucleotide sequencing of DNA fragments from 16 tumorous specimens showed that the major isoform was DDH2 for ESCC. GST expression, however, was only detected weakly in 24 patients (16.6%). For patients with ESCC, DDH overexpression was positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX-2 expression, and inversely correlated with GST and nm23-H1 expressions, but not related to mdr-1 or HER-2/neu expressions. As compared to DDH overexpressed group, patients with low DDH expression had significantly lower incidence of tumor recurrences and better survival (p 0.026). Using univariate analysis, prognostic factors included tumor stage, number of metastatic lymph nodes, cell differentiation, lymphovascular invasion and expressions of DDH and nm23-H1. Multivariate analysis showed significant correlation of tumor stage, number of metastatic lymph nodes and nm23-H1 expression with patient’s survival. In conclusion, inverse expressions of DDH and GST may be associated with carcinogenesis and disease progression for ESCC patients, but their biological function and pathophysiological regulation in tumors require additional studies. © 2004 Wiley-Liss, Inc.

Background Esophageal cancer is one of the most aggressive malignancies in the world, and whether multiple therapeutic modalities could improve long-term survival remains controversial. Recent studies have shown an increase of cyclooxygenase-2 (COX-2) expression in various malignancies, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods From 1993 to 1997, tissue samples from 96 patients with ESCC who underwent esophagectomy at our institution were collected for analysis. Cyclooxygenase-2 expression was examined by immunohistochemical staining, and further confirmed by Western blot analysis on six frozen tissues. Clinicopathologic data were analyzed to verify the significance. Results Cyclooxygenase-2 immunoreactivity was detected in 59 of 96 ESCC specimens (61%), and COX-2 overexpression (COX-2 high) was observed in 49% (47 of 96) of ESCCs. Statistical differences between COX-2 high and COX-2 low were found with respect to the status of distant metastasis (M factor) ( p = 0.035) and tumor stage ( p = 0.04). The survival was not significantly different between patients with and without COX-2 overexpression ( p = 0.43). Using the Cox regression analysis, only the N factor ( p = 0.0034) and M factor ( p = 0.0325) were independent prognostic factors. Conclusions Our results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with fewer metastases and less advanced stage, but had no impact on survival. The status of local or distant lymph node metastasis was the most important prognostic factor. The biological role and pathophysiologic regulation of COX-2 overexpression in ESCC deserve further investigation.

Sinonasal organized hematoma (SOH) is an uncommon benign entity with locally aggressive behavior. The conventional approach is complete resection. This approach, however, can cause massive hemorrhage and mortality in our patient due to a ruptured internal carotid artery (ICA) aneurysm hidden inside the SOH. To the best of our knowledge, this is the first case of a huge SOH with skull base invasion caused by a hidden ICA aneurysm, which usually would not be large enough to result in a sinonasal mass lesion. This case suggests that the possibility of an aneurysm should always be considered if a SOH is suspected, especially when it is huge and close to the ICA. Surgical resection may not be the first therapeutic choice unless the differential cause of a hidden aneurysm can be excluded.

Background Recent studies showed that interleukin-6 (IL-6) played a role in tumor development. However, available information about the prognostic significance of IL-6 and IL-6 receptors (IL-6R) for oral squamous cell carcinoma (OSCC) is limited. Methods Eighty-six patients with OSCC were enrolled. Immunohistochemical staining was used to determine IL-6R expression and in-situ hybridization for IL-6 mRNA transcripts in surgical specimens. Clinicopathologic correlation was evaluated by chi-square test and survival by log rank test. Results Expression rates of IL-6R and IL-6 mRNA transcripts in tumor specimens were 73.3% and 54.7%, much higher than those in nontumor mucosa (p < .001). IL-6R overexpression was associated with larger tumors and more advanced histologic grade (p < .05). The presence of IL-6 mRNA transcripts was inversely correlated with distant metastasis, lymph node involvement, and second primary SCC (p < .05) and predicted better survival (p = .007). Conclusions IL-6-IL-6R coexpression was rather high in OSCC, and IL-6 mRNA transcript expression might influence patient survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional investigation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 850–858, 2002

Background The definite etiology of epiretinal membrane (ERM) is unknown. Clinically, ERM may cause metamorphopsia and decreased vision during the disease exacerbation. Several theories of pathogenesis emphasize a glial tissue origin. However, in some studies, surgically removed ERM specimens were found to contain retinal pigment epithelial (RPE) cells. The actual mechanism by which RPE cells gain access into the inner retina and what roles they play in the formation of ERM remain controversial. The purpose of this study was to evaluate the incidence of RPE cells in ERM and discuss the possible mechanisms. Methods A retrospective review of the histological findings in 23 surgically removed specimens of ERM was done. The samples were studied using light microscopy and immunohistochemistry. Results Glial cells were the main components in all 23 cases, and RPE cells were found in five of the specimens. Two of these five cases were clinically diagnosed as idiopathic macular pucker, whereas the other three cases were identified as macular pucker associated with previous retinal detachment. A much higher density of myofibroblasts was noted in these five specimens than in the other 18 cases. Conclusion The incidence of RPE cells found in ERM is 21.7% (5 out of 23 specimens). A strong association between RPE cells and myofibroblasts in cases of ERM with or without retinal detachment indicates that RPE cells may contribute to the formation of ERM via a wound healing process.

Summary Objectives Management of cN0 neck, elective neck dissection (END) or observation, remains controversial for T1–2 oral squamous cell carcinoma (OSCC). To allow for the safe observation of cN0 neck, it is mandatory to define predictors with high negative predictive value (NPV) for cervical lymph node (LN) status. Materials and Methods Pathologic re-evaluation was performed in tumors of 253 consecutive patients with T1–2, cN0 OSCC. The predictive roles of pathologic parameters for cervical LN status in guiding neck management were investigated. Results Cervical LN metastasis (LN+) occurred at a similar rate between observation and END groups (20.8% vs. 22.2%, p = 0.807), indicating poor discriminatory value for cervical LN status by clinical judgment. Compared with T classification, tumor thickness and differentiation, PNI/LVI (perineural invasion/lymphovascular invasion) demonstrated the highest NPV (85.5%). Hypothetically using PNI/LVI status to guide neck management, a dramatic reduction in overtreatment rate could be achieved (54.2% to 20.2%), with a minimal increase in undertreatment rate (6.3% to 9.9%). In patients without PNI or LVI (PNI/LVI−), the ultimate neck control rate (96.9% vs. 96.3%, p = 1.000) and 5-year disease-specific survival rate (91.1% vs. 92.8%, p = 0.863) were equivalent between observation and END. However, a significantly higher incidence of neck recurrence was found with observation (16.9% vs. 6.5%, p = 0.031), with 93.8% occurring within one year and 73.3% being successfully salvaged. Conclusion Observation under close follow-up for the first year is appropriate in T1–2, cN0 OSCC without PNI or LVI, for the achievement of equivalent ultimate neck control and 5-year disease-specific survival rates compared with END.

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy. (Otolaryngol Head Neck Surg 1999;121:622-6.)

OBJECTIVE: Recently, an association between viral infection and the development of esophageal carcinoma has been reported, particularly the human papilloma virus (HPV) and Esptein-Bar virus (EBV). However, geographic variation in carcinogenesis is realized. In this study, we investigate the viral carcinogenesis and the biologic effect of viral infection on esophageal squamous cell carcinoma (ESCC) in Taiwan. METHODS: To determine the association of viral infection (EBV and HPV) with ESCC, we applied polymerase chain reaction (PCR), immunohistochemistry, and in situ hybridization (ISH) to examine 119 surgical specimens from different sites of esophagus in 31 ESCC patients. Additionally, an immunoperoxidase method was used to detect EBV latent membrane protein-1 (LMP-1), p53, CD45RO (UCHL-1), Fas ligand (Fas L), and RNA ISH with oligonucleotide sequences was used to detected interleukin-6 (IL-6) mRNA. RESULTS: By PCR, EBV DNA was detected in 11 cases (35.5%). Expression of EBERs in ESCC was further confirmed with ISH. Nonetheless, no LMP-1 expression was detected. On the other hand, human papillomavirus (HPV) was identified in only one case (3.2%) of ESCC. Furthermore, HPV was located by ISH in the distant normal region rather than in tumor cells. In EBV-positive cases, accumulation of p53 protein was detected in 10 lesions (91%); CD45RO+ lymphocytes together with expressions of FasL and IL-6 were respectively identified in 100%, 63.6%, and 54.5% of 11 EBV-positive lesions. Interestingly, in the EBV-negative cases (n = 20), p53 protein was detected in 40% of lesions; CD45RO 30%; FasL 50%, and IL-6 10%. CONCLUSIONS: In this study, no correlation was found between the presence of EBV in ESCC and the patients’ age, sex, as well as survival. Although our results indicate that EBV could be associated with ESCC, the clinical role of EBV in ESCC remains to be determined.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is rather common among the Chinese, but the therapeutic outcome is dismal. Knowledge of the prognostic factors in cancerous patients may influence therapeutic strategy. However, systemic analyses of clinicopathological and biological factors for patients with ESCC are few, and the results are controversial. METHODS: Between 1985 and 1996, 117 patients undergoing en bloc esophagectomy and gastric substitution were enrolled. None had neoadjuvant treatment. Postoperative adjuvant therapy was provided for patients at and beyond stages IIa. Clinical responses were followed routinely. Flow cytometry was used to measure DNA ploidy and synthesis-phase fraction (SPF) of the resected esophageal tissues from all patients. Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen (PCNA), epidermoid growth factor receptor (EGFR), HER-2/neu, and p53 in the pathological sections. Clinical correlation was evaluated by χ2 with Fisher’s exact test, and survival by log-rank test. RESULTS: The overall survival rates were 74% for 1 yr, 48% for 3 yr, and 38% for 5 yr. TNM tumor staging, the number of diseased lymph nodes (N ≤ 3 or N > 3), degree of cell differentiation, DNA ploidy, SPF, and lymphovascular invasion were more useful than biological markers, such as PCNA, EGFR, HER-2/neu, and p53, for the prognosis of ESCC. Multivariate analysis revealed significant correlation of tumor staging and number of diseased lymph nodes with patient survival after surgery. CONCLUSIONS: En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.