• Title/Summary/Keyword: Poor prognostic patients

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Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

  • Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5469-5475
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    • 2012
  • Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Clinical Observation on The Left and Right Facial Palsy (${\cdot}$右側 口眼와斜 患者에 對한 臨床的 考察)

  • Lim, Jin-Ki;Lim, Gyu-Sang;Hwang, Choong-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.10 no.1
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    • pp.383-402
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    • 1997
  • The author analyzed 155 cases of Facial Palsy, excluding lesions caused by cerebrovascular attacks, who were treated in the Kwang-ju Oriental Medical Hospital of Wonkwang University from March 1996 to September 1996. I've examined the 155 cases in the view of the etiologic distributions, the age, the relationship of the sex and paralytic side, attended symptoms and analyzed 95 cases who were treated over ten times in the view of the ratio of recovery according to the age, anatomic focus, the relations of sex and paralytic side. The following results are obtained. 1. The ratio of punghan(風寒) was $20.64\%$(32 cases), overwork was $18.70\%$(29 cases), stress was $6.44\%$(10 cases), excessive drinking was $3.23\%$(5 cases), teeth pain was $1.93\%$(3 cases), and idiopathy was $38.05\%$(59) and etc. 2. The ratio of stylomastoid pain was $15.48\%$(24 cases), auricular pain was $10.32\%$(16 cases), headache was $4.51\%$(7 cases), eyedried was $4.51\%$(7 cases), taste paralysis was $2.57\%$(4 cases), tinnitus was $2.57\%$(4 cases) and non-significant symptoms was $50.97\%$(79) and etc. 3. The ratio of 2th and 5th decade were $20.00\%$(31 cases), 4th decade was $18.71\%$(29 cases), 3th decade was $16.71\%$(26 cases), 6th decade was $11.61\%$(18 cases), teenagers in $5.81\%$(9 cases), over seventy and under teenagers were $3.23\%$(5 cases), and infant was $0.65\%$(1 case). 4. The ratio of the male-right was $28.39\%$(44 cases), female-right was $25.82\%$(40 cases), male-left was $23.23\%$(36 cases), female-left was $20.65\%$(32 cases) and male-both side was $1.94\%$(3 cases) in order. 5. Topographically, The ratio of the infrachordal lesion was $72.90\%$(113 cases), transgeniculate lesion was $16.13\%$(25 cases), suprageniculate lesion was $5.81\%$(9 cases), infrastapedial lesion was $3.87\%$(6 cases) and suprastapedial lesion was $1.29\%$(2 cases) in order. 6. When we examined the degree of recovery about the 95 patients who were treated over ten times after on attack, normal improvement was seen in $46.32\%$(44 cases), excellent in $7.37\%$(7 cases), good in $12.63\%$(12 cases), fair in $13.68\%$(13 cases), poor in $20.00\%$(19 cases). The total remedial value of the 95 patients who were treated over ten times was revealed $61.58\%$. 7. When we examined the 95 patients who were treated over ten times, the remedial value of the infant was $50.00\%$, under teenagers $43.75\%$, teenagers $37.50\%$, 2th decade $56.82\%$, 3th decade $64.06\%$, 4th decade $55.00\%$, 5th decade $73.53\%$, 6th decade $77.50\%$, over seventieth $68.75\%$. The remedial value of 3th decade, 5th decade, 6th decade, 7th decade and over seventieth were higher than the total remedial value($61.58\%$) 8. In the point of topographical lesion, when we examined the 95 patients who were treated over ten times, the remedial value of infrachordal lesion was $66.78\%$, infrastapedial lesion $58.33\%$, suprastapedial lesion $50.00\%$, transgeniculate lesion $48.44\%$, suprageniculate lesion $31.25\%$, in order. Only the remedial value of Infrachordal($66.78\%$) was higher than the total remedial value($61.58\%$). 9. In the point of the relationship of the sex and the paralytic side, when we examined the 95 patients who were treated over ten times, the remedial value of male-left was $57.29\%$, male-right $61.54\%$, male-both side $58.33\$%, female-left $57.81\%$ and female-right $68.27\%$. Only the remedial value of female-right($68.27\%$) was higher than the total remedial value($61.58\%$). These results demonstrated that in the point of prognostic view there was more concerned with the topographical lesion, body condition than the traditional rule of sex-paralytic relationship that man is awed left paralysis and woman right paralysis.

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Triple Negative Status is a Poor Prognostic Indicator in Chinese Women with Breast Cancer: a Ten Year Review

  • Ma, K.K.;Chau, Wai Wang;Wong, Connie H.N.;Wong, Kerry;Fung, Nicholas;Lee, J.T. Andrea;Choi, L.Y. Catherine;Suen, Dacita T.K.;Kwong, Ava
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2109-2114
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    • 2012
  • Background: Ethnic variation in tumor characteristics and clinical presentation of breast cancer is increasingly being emphasized. We studied the tumor characteristics and factors which may influence the presentation and prognosis of triple negative breast cancers (TNC) in a cohort of Chinese women. Methods: A prospective cohort of 1800 Chinese women with breast cancer was recruited in a tertiary referral unit in Hong Kong between 1995 and 2006 and was followed up with a median duration of 7.2 years. Of the total, 216 (12.0%) had TNC and 1584 (88.0%) had non-TNC. Their clinicopathological variables, epidemiological variables and clinical outcomes were evaluated. Results: Patients with TNC had similar age of presentation as those with non-TNC, while presenting at earlier stages (82.4% were stage 1-2, compared to 78.4% in non-TNC, p=0.035). They were likely to be associated with grade 3 cancer (Hazard Ratio(HR)=5.8, p<0.001). TNC showed higher chance of visceral relapse (HR=2.69, p<0.001), liver metastasis (HR=1.7, p=0.003) and brain metastasis (HR=1.8, p=0.003). Compared with non-TNC group, TNC had similar 10-year disease-free survival (82% vs 84%, p=0.148), overall survival (78% vs 79%, p=0.238) and breast cancer-specific mortality (18% vs 16%, p=0.095). However, TNC showed poorer 10-year stage 3 and 4 specific survival (stage 3: 53% vs. 67%, p=0.010; stage 4: 0% vs. 40%, p=0.035). Conclusions: Chinese women with triple negative breast cancer do not have less aggressive biological behavior compared to the West and presentation at a later stage results in worse prognosis compared with those with non triple negative breast cancer.

Prognostic Significance of $O^6$-MGMT and Promotor Hypermethylation in Patients with Soft Tissue Sarcomas (연부조직육종 환자에서 $O^6$-MGMT 와 촉진자 과메틸화의 예후적 중요성)

  • Suh, Jeung-Tak;Kim, Jeung-Il;Oh, Jong-Seok;Choi, Kyung-Un
    • The Journal of the Korean bone and joint tumor society
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    • v.15 no.1
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    • pp.13-25
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    • 2009
  • Purpose: The DNA repair protein, $O^6$-methylguanine-DNA methyltransferase (MGMT), removes alkyl adducts from the $O^6$ position of guanine. Epigenetic inactivation of MGMT has been found in human neoplasia and considered one of the implicated factors in chemoresistance. Materials and Methods: Sixty-two patiensts with soft tissue sarcomas (STS) were analyzed for the status of MGMT protein expression by immunohistochemistry and the promoter hypermethylation of the MGMT gene using methylation-specific PCR. Result: The loss of MGMT expression was found in 20 cases (32.3%) of total 62 STS. MGMT promoter hypermethylation rate was 25.0% (11/44 cases). The loss of MGMT expression showed significant association with high AJCC stage, high FNCLCC grade, and aggressive behavior. However,when the group who received chemotherapy was analyzed (n=27), loss of MGMT expression was correlated with worse survival in multivariate analysis (p=0.024). MGMT promoter hypermethylation is associated with high FNCLCC grade. MGMT promoter hypermethylation status had a strong correlation with loss of MGMT expression (p=0.000). Conclusion: Our results suggest that MGMT promoter hypermethylation and loss of MGMT expression had a tendency to be associated with poor prognosis and that loss of MGMT protein expression is frequently occurs via MGMT promoter hypermethylation.

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TLE1: A New Molecular Target of Synovial Sarcoma (활액막 육종에서 새로운 종양 표지자로서 TLE1의 가치)

  • Cho, Eun-Yun;Kim, Dong-Wook;Seo, Sung-Wook
    • The Journal of the Korean bone and joint tumor society
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    • v.15 no.1
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    • pp.7-12
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    • 2009
  • Purpose: This study was aimed to assess TLE1 as a target molecule of synovial sarcoma. Method: We obtained tissue samples and clinical data from 36 patients who were diagnosed and treated for synovial sarcoma in our hospital. Immunohistochemical staining was performed to detect the expression of TLE1 in synovial sarcoma and normal tissues such as fat, skeletal muscle, peripheral nerve, vascular endothelium, and epithelium. Univariate survival analysis was performed to find whether overexpression of TLE1 is correlated to poor prognosis. Results: TLE1 was expressed in 35 (97%) cases (grade 1 was 5 cases, grade 2 was 28 cases, grade 3 was 2 cases.). Normal tissues from mesenchymal origin did not express TLE1. However, epithelial and endothelial cells showed weak expression (grade 1) of TLE1. The level of TLE1 expression did not have any prognostic significance according to univariate survival analysis. Conclusion: TLE1 may be a new molecular target of synovial sarcoma that differentiates synovial sarcoma from normal mesenchymal cells.

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Current Trends in the Treatment of Ankle Ligament Injuries: Analysis of the Korean Foot and Ankle Society (KFAS) Member Survey (족관절 인대 손상 치료 동향: 대한족부족관절학회 회원 설문조사 분석)

  • Cho, Byung-Ki;Cho, Jaeho;Lee, Myoungjin;Lee, Jun Young;Bae, Su-Young;The Academic Committee of Korean Foot and Ankle Society,
    • Journal of Korean Foot and Ankle Society
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    • v.26 no.1
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    • pp.22-29
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    • 2022
  • Purpose: Despite continuous updates of standard treatment guidelines for acute ankle sprain and chronic ankle instability (CAI), in practice preferred treatment protocols vary widely. Based on a Korean Foot and Ankle Society (KFAS) member survey, this study reports current trends in the management of ankle ligament injuries. Materials and Methods: A web-based questionnaire containing 34 questions was sent to all KFAS members in September 2021. Questions mainly addressed clinical experience and preferences for the diagnosis and treatment of ankle ligament injuries. Answers with a prevalence of ≥50% among respondents were considered to reflect tendencies. Results: Eighty-four of the 550 members (15.3%) responded. Answers that showed a tendency were as follows: commonest additional image study (ultrasound), conservative treatment modality (immobilization, oral medication), frequency of surgical treatment (<5 cases per annum), most important factor when deciding on surgical treatment (activity level, e.g., occupation or sport), and commonest surgical procedure (open ligament repair). Answers that showed a tendency for CAI were as follows: most important symptom (repeated sprain, giving way), radiological factors (talar tilt, osteochondral lesion, anterior talar translation), and patient factors (occupation, sports activities, recurrent instability after surgery, etc.). For decision making regarding surgical treatment and method, the most preferred surgical procedure was the modified Broström procedure, and the most common repair technique was suture anchor technique. The following were considered poor prognostic factors; generalized laxity, failed previous surgery, cavovarus, severe mechanical instability, heavy work, obesity, and dissatisfaction after surgery because of residual pain. Conclusion: This study updates information regarding current trends in the management of ankle ligament injuries in Korea, and reveals consensus opinions and variations in approaches to patients with an acute or chronic injury. The divergence of approaches identified indicates the need for further studies to determine standard guidelines and long-term results.

Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers

  • Moonjung Lee;Jaekwon Seok;Subbroto Kumar Saha;Sungha Cho;Yeojin Jeong;Minchan Gil;Aram Kim;Ha Youn Shin;Hojae Bae;Jeong Tae Do;Young Bong Kim;Ssang-Goo Cho
    • International Journal of Stem Cells
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    • v.16 no.2
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    • pp.215-233
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    • 2023
  • Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

The Usefulness of Postoperative Pinhole Bone Scintigraphy in the Assessment of Prognosis after Multiple Drilling or Vascularized Bone Graft in Patients with Avascular Necrosis of Femoral Head (다발성 천공술 및 혈관 부착 골이식술을 시행한 대퇴골두 무혈관성 괴사의 예후: 수술 후 바늘구멍 골신티그라피의 유용성)

  • Chung, Yong-An;Kim, Sung-Hoon;Chun, Kyung-Ah;Park, Young-Ha;Sohn, Hyung-Seon;Chung, Soo-Kyo;Song, Mun-Kab
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.4
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    • pp.405-412
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    • 1999
  • Purpose: It is important to evaluate the healing process of avascular necrosis (AVN) involving femoral head after treatment. The purpose of this study was to assess the usefulness of pinhole bone scintigraphy in the AVN of femoral head after surgery. Materials and Methods: We analyzed the changing pattern of pinhole bone scintigram in 21 femoral heads of 16 patients (14 lesions/11 male, 7 lesions/5 female, mean age: 39.4 yrs) before and after multiple drilling or vascularized bone grafting for AVN of the femoral head. In all patients, pre-operative scintigrams were obtained at 1 to 3 months before treatment and the first post-operative scintigrams were obtained at 1 to 3 months after treatment. All patients were followed for 2 to 4 years after operation. Results: The findings of the pinhole scintigrams were divided into three patterns: 1) curvilinear, 2) scattered spotty and 3) undetermined. The 10 of 11 lesions with curvilinear pattern had good postoperative clinical and radiological follow-up findings. However, all 6 lesions with scattered spotty pattern showed poor postoperative findings, which necessitated total hip joint replacement. Of the 4 lesions with undetermined pattern, 2 required total hip joint replacement. There was significant difference in postoperative prognosis between the curvilinear and scattered spotty patterns (p<0.05). Conclusion: We conclude that the pattern of pinhole bone scintigram obtained within 1 to 3 months after multiple drilling or vascularized bone graft operation is a useful prognostic indicator in the AVN of femoral head.

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Clinical Characteristics and Prognostic Factors of Nasopharyngeal Cancer (비인강암의 임상적 고찰과 예후인자)

  • Bai, Chang-Hoon;Seo, Young-Jung;Ye, Sang-Baik;Choi, Young-Ho;Kim, Yong-Dae;Song, Si-Youn
    • Journal of Yeungnam Medical Science
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    • v.22 no.1
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    • pp.72-80
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    • 2005
  • Background: Nasopharyngeal cancer is a rare disease with a relatively poor prognosis because it tends to be diagnosed at an advanced stage. The aim of this study was to establish the clinical characteristics of nasopharyngeal cancer. Materials and Methods: The medical records of 54 patients with nasopharyngeal cancer from January 1993 to December 2002 were reviewed retrospectively. Forty one cases were male (75.9%) and thirteen were female (24.1%). The average age was of 46.9 (range 16 to 78 years) years. The majority of patients (79.6%) were diagnosed in the advanced stage. The most common complaints were a neck mass (55.5%) and the WHO type III (53.7%) was the most frequent histological type. Results: The cumulative survival rate for a 5-year period was 46.5% and the T stage, N stage, pathologic type, and clinical stage were not significantly related to the survival rate. Sixteen of 54 (31.5%) cases presented with a distant metastasis of the bone, lung, brain, spine, and liver, and six cases (11.1%) presented with a locoregional recurrence. Conclusion: TNM staging is not appropriate for predicting survival rate of nasopharyngeal carcinoma patients. Therefore, a newer staging system, which includes new factors, is needed to predict the prognosis.

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Expression of Hypoxia-inducible Factor-1 $\alpha$ in Esophageal Squamous Cell Carcinoma: Relationship to Prognosis and Tumor Biomarkers (식도 편평세포암에시 Hypoxia-inducible Factor-1 $\alpha$의 발현: 예후와 종양표지자와의 상관성)

  • 양일종;김종인;이해영;천봉권;조성래
    • Journal of Chest Surgery
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    • v.37 no.8
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    • pp.691-701
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    • 2004
  • Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.