Chih-Yen Chien

Kikuchi's disease: A review and analysis of 61 cases

OBJECTIVEnKikuchis disease (KD), or histiocytic necrotizing lymphadenitis, is a rare self-limiting disorder that typically affects the cervical lymph nodes. It has occasionally been misdiagnosed as malignant lymphoma or another serious diseases; hence, clinicians should be made more aware of this disease.nnnMETHODSnFrom January 1986 to January 2001, a series of 61 patients who underwent a biopsy of a cervical lymph node and proved histologically to have KD were enrolled in this study. We retrospectively reviewed the clinical records and pathologic parameters of each patient. The patients were followed up from 6 months to 14.3 years (mean, 6.9 years).nnnRESULTSnThere were 34 women and 27 men (1.26:1 ratio; age range, 6 to 46 years; mean age, 21 years). The affected cervical lymph nodes were commonly located in the posterior cervical triangle (54 of 61, or 88.5%). Unilateral and bilateral cervical lymph nodes were affected in 54 and 7 patients, respectively. The dimensions of affected lymph nodes were commonly in the range of 0.5 to 4 cm (57 of 61, or 93.4%). In 2 patients, the size of the enlarged lymph nodes was greater than 6 cm. Leukopenia was observed in 14 patients (23%); fever, in 18 patients (29.5%). Five patients had a past history of tuberculosis. Two patients developed systemic lupus erythematosus, 1 month and 5 years later, respectively. The cervical lymphadenopathy usually resolved without any medical treatment within 6 months after definite diagnosis was made. In 3 patients, the enlarged lymph nodes eventually disappeared after more than 1 year. No recurrence has since been noted.nnnCONCLUSIONnThe results of this study support the theory that KD is a self-limiting disorder that does not require any specific management. The female predominance was not as striking as in the studies performed in Western countries. We suggest that the patients with KD require a systemic survey and regular follow-up for several years; 2 of our patients developed systemic lupus erythematosus. An effective communication between the otolaryngologist and pathologist is needed because the clinical and pathologic characteristics of KD are essential in making an accurate diagnosis.

Fibulin-3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity

Nasopharyngeal carcinoma (NPC) is known for its highly metastatic character. Recent advances in diagnosis and treatment have not improved the high mortality rate that is attributable to early metastasis. Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. We demonstrate comprehensively that fibulin‐3 is down‐regulated in NPC. Loss of fibulin‐3 expression is significantly correlated with advanced tumour and lymph node‐metastasis stages, and indicates a poor 5‐year survival rate. Functionally, fibulin‐3 has the ability to suppress cell migration and invasion in NPC cancer cells by decreasing the activity of phospho‐AKT. Conversely, its depletion by fibulin‐3‐mediated siRNAs may elevate phospho‐AKT activity and significantly enhance the ability of NPC cancer cells to migrate and invade. Consistent with this negative association between fibulin‐3 and phospho‐AKT, their expression levels are inversely correlated in NPC specimens by immunohistochemical analysis. Thus, lower fibulin‐3 expression is an important indicator of poor survival. It may also contribute to the development of new therapeutic strategies to block the PI3K/AKT pathway in NPC cancer cells. Copyright

Changing Quality of Life in Patients with Advanced Head and Neck Cancer after Primary Radiotherapy or Chemoradiation

Objective: The purpose of this study was to investigate the longitudinal changes in quality of life (QoL) for patients with advanced stage (stage III or IV) head and neck squamous cell carcinoma (HNSCC) following primary radiotherapy (RT) or concomitant chemoradiotherapy. Methods: From January 2001 to January 2003, 149 patients with advanced HNSCC were enrolled. The data pertaining to their QoL were collected using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EORTC Head and Neck Module (QLQ-H&N35) before and 1 year after RT. Results: Sixty-eight (46%) patients dropped out during the study period. Thirty-nine (57%) of them died of cancer. Those who were older, stage IV, treated by RT alone, or had worse pretreatment EORTC QoL scales were significantly more likely to drop out. For those completing the study, only the problems of swallowing, dry mouth, and sticky saliva were found to become more serious with both statistical (p < 0.05) and clinical (difference >10 points) significance 1 year after RT. Those subjects with cancer at the hypopharynx/larynx had a 3.3-fold higher probability to report an improvement in global QoL (95% confidence interval, CI: 1.11–6.82) than those with cancer at the oral cavity/oropharynx. Those alive without cancer 1 year after RT had a 3.6-fold higher probability to report an improvement in global QoL (95% CI: 1.32–7.13) than those alive with cancer. Conclusion: The study showed a high dropout rate in this longitudinal QoL study for patients with advanced HNSCC. Pretreatment cancer sites and living with cancer or not after treatment significantly affected the change in global QoL 1 year after RT.

High expression of CD105 as a prognostic predictor of early tongue cancer.

Objectives: The purpose of this article is to investigate the expressions of vascular endothelial growth factor (VEGF) and endoglin (CD105) in the biopsy tissues of squamous cell carcinoma of the tongue in early tumor stages and their relationship with the clinicopathologic features.

CLINICOPATHOLOGIC SIGNIFICANCE OF CD105 EXPRESSION IN SQUAMOUS CELL CARCINOMA OF THE HYPOPHARYNX

Induction of angiogenesis is a key process in tumor growth and metastasis. We studied the CD105 (endoglin) and vascular endothelial growth factor (VEGF) in hypopharyngeal cancer to evaluate their clinicopathologic significance.

Changes in quality of life of head-and-neck cancer patients following postoperative radiotherapy

The purpose of this study was to investigate the longitudinal changes in quality of life (QoL) for 77 head-and-neck squamous cell cancer (HNSCC) patients receiving postoperative radiotherapy (RT). The data pertaining to their QoL were collected using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EORTC Head and Neck Module (QLQ-H&N35) before and two years after postoperative RT. The differences in all the QLQ-C30 scales between the two time points were not statistically (p<0.01) or clinically (difference ≧+10 points) significant. Of all the scales in the QLQ-H&N35, only problems in social eating, teeth, dry mouth, and sticky saliva became worse with both statistical and clinical significance. Clinical cancer stage and marital status were the only variables significantly associated with the change in global QoL. The subjects with stage IV disease (5.0-fold) and those with a spouse (5.5-fold) had a lower risk of reporting negative changes in global QoL. The study indicates that some individual HNSCC patients, after receiving postoperative RT, suffered from a deterioration of QoL scales, especially in some specific head-and-neck symptoms. Meanwhile, we found some patients, especially those with more advanced HNSCC, might have developed somewhat tougher coping abilities to deal with the adverse effects of adjuvant RT on their global QoL.

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

BackgroundThis study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1) expression on response to cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) patients.MethodsFifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records.ResultsThe 12-month progression-free survival (PFS) and 2-year overall survival (OS) rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p < 0.001) and 2-year OS (74.2 vs. 44.4%, p = 0.023) rates. Multivariate analysis showed that for patients who did not chew betel nuts and had low expression of ERCC1 were independent predictors for prolonged survival.ConclusionsOur study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma

Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p<0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p<0.001), positive N status (p<0.001), advanced TNM stage (p<0.001) and male gender (p=0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p<0.001), advanced T stage (p<0.001), positive N status (p<0.001) and advanced TNM stage (p<0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p<0.001) and osteopontin immunostaining was marginally significant for survival (p=0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.

Overexpression of Rap-1A indicates a poor prognosis for oral cavity squamous cell carcinoma and promotes tumor cell invasion via Aurora-A modulation.

The functions of Rap-1A in oral carcinogenesis are largely unexplored. In this study, we examined the expression of Rap-1A at different malignant stages of oral cavity squamous cell carcinoma (OCSCC). Semiquantitative RT-PCR, quantitative RT-PCR, and Western blotting were used to evaluate Rap-1A mRNA and protein expressions, respectively, in paired OCSCC patient specimens. To determine the possible correlation between Rap-1A expression and various clinical characteristics, 256 samples from patients with OCSCC were evaluated by immunohistochemical staining. Strong Rap-1A expression was a significant prognostic marker and predictor of aggressive OCSCC. The overall and disease-specific 5-year survival rates were significantly correlated with strong expression of Rap-1A (P < 0.001). Functionally, overexpressed Rap-1A could promote oral cancer cell migration and invasion by Transwell chambers and wound healing assay. Conversely, the suppression of Rap-1A expression using Rap-1A-mediated siRNA was sufficient to decrease cell motility. Furthermore, our data also illustrated that Aurora-A could not only induce mRNA and protein expressions of Rap-1A for enhancing cancer cell motility but also co-localize and form a complex with Rap-1A in the oral cancer cell line. Finally, immunohistochemical staining, indirect immunofluorescence, and Western blotting analysis of human aggressive OCSCC specimens revealed a significantly positive correlation between Rap-1A and Aurora-A expression. Taken together, our results suggest that the Aurora-A/Rap-1A pathway is associated with survival, tumor progression, and metastasis of OCSCC patients.

Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma

BackgroundHypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC).MethodsThe study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays.ResultsWe found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9u2009years (range, 26–87u2009years). The mean follow-up period was 67u2009months (range, 2–171u2009months). High EPOR expression was significantly correlated with advanced T classification (pu2009<u20090.001), advanced TNM stage (pu2009<u20090.001), and positive N classification (pu2009=u20090.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (pu2009=u20090.0011) and 5-year disease-specific survival rate (pu2009=u20090.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates.ConclusionsHigh EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future.