• Korean Journal of Radiology
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• 제23권11호
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• pp.1078-1088
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• 2022

Objective: To develop and validate a model using radiomics features from apparent diffusion coefficient (ADC) map to diagnose local tumor recurrence in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: This retrospective study included 285 patients (mean age ± standard deviation, 62 ± 12 years; 220 male, 77.2%), including 215 for training (n = 161) and internal validation (n = 54) and 70 others for external validation, with newly developed contrast-enhancing lesions at the primary cancer site on the surveillance MRI following definitive treatment of HNSCC between January 2014 and October 2019. Of the 215 and 70 patients, 127 and 34, respectively, had local tumor recurrence. Radiomics models using radiomics scores were created separately for T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and ADC maps using non-zero coefficients from the least absolute shrinkage and selection operator in the training set. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of each radiomics score and known clinical parameter (age, sex, and clinical stage) in the internal and external validation sets. Results: Five radiomics features from T2WI, six from CE-T1WI, and nine from ADC maps were selected and used to develop the respective radiomics models. The area under ROC curve (AUROC) of ADC radiomics score was 0.76 (95% confidence interval [CI], 0.62-0.89) and 0.77 (95% CI, 0.65-0.88) in the internal and external validation sets, respectively. These were significantly higher than the AUROC values of T2WI (0.53 [95% CI, 0.40-0.67], p = 0.006), CE-T1WI (0.53 [95% CI, 0.40-0.67], p = 0.012), and clinical parameters (0.53 [95% CI, 0.39-0.67], p = 0.021) in the external validation set. Conclusion: The radiomics model using ADC maps exhibited higher diagnostic performance than those of the radiomics models using T2WI or CE-T1WI and clinical parameters in the diagnosis of local tumor recurrence in HNSCC following definitive treatment.

• Journal of Chest Surgery
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• 제41권1호
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• pp.68-73
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• 2008

배경: 원발성 비소세포성 폐암에서 종격동 림프절 전이는 중요한 예후인자 중의 하나이다. 이 연구는 원발성 비소세포성 폐암으로 수술 받은 환자에서 폐엽에 따른 종격동 림프절 전이 양상을 파악하여 적극적인 종격동 림프절 절제술을 시행하고 그로 말미암아 병기 결정에 도움이 되고자 시행하였다. 대상 및 방법: 1998년 1월부터 2005년 12월까지 원발성 폐암으로 완전한 종격동 림프절 절제술과 함께 근치적 폐 절제술을 시행받았던 293명의 환자를 대상으로 의무기록을 토대로 후향적 연구를 시행하였다. 환자의 평균나이는 $63.0{\pm}8.3$세($37{\sim}88$세)였으며 남자가 220명(75.1%)이었다. 원발성 종양과 림프절의 분류는 Mountain등이 발표한 TNM 병기를 근거로 하였으며 조직학적 분류는 WHO 분류를 기초로 하였다. 통계 처리는 Fisher's exact test와 chi-square test를 사용하였고 p 값이 0.05 미만일 경우 의의 있는 결과로 받아들였다. 결과: 전체 환자 중에서 폐엽절제술은 180명, 폐이엽절제술은 50명, 소매폐엽절제슬은 10명, 전폐절제술은 53명에서 시행되었다. 수술 후 폐종양의 병리학적 진단은 선암(adenocarcinoma)이 124명, 편평세포암(squamous cell carcinema)이 138명, 선편평세포암(adenos-quamous cell carcinoma)이 14명이었으며 카르시노이드종양(carcinoid tumor) 1명, 대세포암(large cell carcinoma) 8명, 암육종(carcinosarcoma) 1명, 점액표피양암(mucoepiderrnoid carcinoma) 2명, 미분류된 암이 5명이었다. 술 후 TNM 병기는 IA가 51명, IB가 98명, IIA가 9명, IIB가 41명, IIIA가 71명, IIIB가 16명, IV가 6명이었다. 전체 환자 중 N2 이상의 병기를 보인 환자는 25.9%(76명)이었고 그 중 우상엽의 병변인 경우 4번 림프절로의 전이가 가장 많았으며 좌상엽의 병변인 경우 4번과 5번, 나머지 폐엽에서는 7번 림프절로의 전이가 가장 많았으나 통계적 의의는 없었고 도약 전이가 전체 환자 중12.3% (36명)에서 발견되었다. 결론: 원발성 비소세포성 폐암의 폐엽에 따른 종격동 림프절 전이 양상은 뚜렷한 규칙이 없으며 도약 전이도 12.3%에서 발생되었으므로 완전한 종격동 림프절 절제술만이 정확한 병기를 결정하는데 도움이 되고 환자의 예후를 결정하는데 중요한 역할을 한다고 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4623-4627
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• 2014

Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권1호
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• pp.11-19
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• 2007

This study was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in tumor and stromal cells of tougue squamous cell carcinoma (SCC). We also wanted to characterize the differences, from the angiogenic aspect, between cancer-associated stromal cells and non-malignant stromal cells. Paraffin-embedded tumor specimens from eleven patients with tongue SCCs were studied. Immunohistochemical staining for VEGFR-1,-2, and -3 was performed on the tumor cells, stromal fibroblasts and tumor-associated macrophages of the specimens. The expression of all 3 receptors was detected in the tumor cells themselves of the biopsy specimens. All 3 receptors were also expressed on stromal cells, except that VEGFR-2 was not expressed in stromal fibroblasts. In radical excision specimens, the staining intensity for VEGFR-1, -2 in the tumor cells and VEGFR-1,-3 in the tumor-associated macrophages was significantly lower than that in the biopsy specimens (P < 0.05). By using the general marker of fibroblast and macrophage, 5B5 and CD68, respectively, we performed double immunofluorescence staining for 5B5 and each VEGFR in the stromal fibroblasts and for CD68 and each VEGFR in the tumor-associated macrophages of the radical excision specimens. We used 4 cases of fibroma and 4 cases of chronic inflammation tissue as the controls. It was found that only each marker was expressed in the control group, however, 5B5/VEGFR-1 and 5B5/VEGFR-3 in the stromal fibroblasts, and CD68/VEGFR-1 and CD68/VEGFR-3 in the tumor-associated macrophages were double stained in the radical excision specimens. Although our study used small number of specimens, the results of our study showed that in tongue SCC, in association with the angiogenesis, the stromal cells showed the activated phenotype and this was different from the nonmalignant stromal cells.

• 대한두경부종양학회지
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• 제14권2호
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• pp.182-190
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• 1998

1) 저자들이 경험한 상악동의 비편평세포암은 선양낭성 암종이 4례로 가장 많았으며, 그 외 선암종 3례, 미분화세포암 3례, 횡문근육종 2례, 골육종 1례, 이행세포암종 1례, 신경내분비세포암종 1례, 섬유성조직구암종이 1례였다. 2) 경부림프절 전이는 총 16례중 횡문근육종 1례와 선양낭성암종 1례에서 있었으며, 모두 종양의 T병기가 T4인 경우였다. 경부림프절 전이가 없었던 경우는 선양낭성 암종1례를 제외하고는 선택적 경부곽청술은 시행하지 않았으며, 추적 관찰도중 원발병소 치료후 경부림프절에서의 잔존암 및 재발은 없었다. 3) 선양낭성암종의 경우, 4례중 3례에서는 수술적 절제를 하였고, 1례에서는 방사선치료후 구제수술을 시행하였으며, 3례가 무병생존 중으로 광범위한 수술적 제거와 더불어 상악신경 하악신경 및 비디안신경을 통한 전파 및 미세잔존암이 의심될 경우 방사선 치료의 병합이 바람직하다고 생각된다. 4) 선암종의 경우 3례중 2례는 low-grade로서 수술과 방사선 치료의 병합요법을 시행하여 무병생존 중이고 1례는 high-grade로서 수술적 절제가 불가능하여 화학요법과 방사선치료의 병합요법후 구제수술을 한 경우로 현재 유병생존 중으로 광범위한 수술적 절제와 더불어 진행된 병기의 경우 방사선 치료의 병합이 바람직하다고 생각된다. 5) 미분화세포암의 경우 3례중 2례는 화학요법 및 방사선 치료후 구제수술을 시행하였고, 1례는 화학요법 및 방사선 치료의 병합요법만을 시행한 경우로 이중 2례가 무병생존 중으로 화학요법 및 방사선 치료에 비교적 잘 반응하며, 절제 가능한 잔존암이 남아 있는 경우 구제수술을 시행하는 것이 바람직하다고 생각된다. 6) 횡문근육종과 골육종의 경우 3례중 2례에서 광범위한 수술적 제거후 방사선치료를 병행하였으며, 현재 무병생존 중이고, 1례는 화학요법과 방사선치료의 병합요법을 시행하였으나 실패하였다. 육종의 경우 광범위한 수술적 절제가 가장 좋은 치료로 사료되며, 미세잔존암이 남아있는 경우는 방사선 치료의 병합이 필요하리라 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7843-7846
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• 2015

Background: Some matrix metalloproteinases (MMPs) are involved in invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on association between stromelysin-2 (ST-2) and invasive behavior of HNSCC. The purpose of this study was to investigate Stromelysin-2 expression by immunohistochemistry. Materials and Methods: This study was conducted on 81 specimens, including 61 HNSCC and 20 non neoplastic epithelium. Sections with 5 micron thickness were prepared and stained with immunohistochemistry technique. Then expression of ST-2 was evaluated according to percentage of stained cells and intensity of staining. Data were analyzed by SPSS (V.21) using Kruskal-Wallis and Tukey tests (P<0.05). Results: The 61 HNSCC specimens were grades I 36.1%, II 34.4% and III 29.5%. The level of ST-2 expressions were moderate (++) and intensive (+++) in 21.3% and 78.7% of tumors, respectively. The ST-2 expression level was only significant between the tumors with grade I and grade III (P=0.016). Tumors presented ST-2 expression with staining intensity of mild 6.6%, moderate 26.2% and strong 67.2%. Staining intensity of ST-2 in grade I tumors was significantly lower than grade II and grade III (P<0.05), and there was no significant difference between grades II and III (P=0.99). Conclusions: According to this study, the expression of ST-2 is associated with histopathological grade and tumor differentiation in HNSCCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권3호
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• pp.166-170
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• 2017

Objectives: To define the risk of occult cervical metastasis of maxillary squamous cell carcinoma (SCC) and the therapeutic value of elective neck dissection (END) in survival of clinically negative neck node (cN0) patients. Materials and Methods: Sixty-seven patients with maxillary SCC and cN0 neck were analyzed retrospectively, including 35 patients with maxillary gingiva and 32 patients with maxillary sinus. Results: Of 67 patients, 10 patients (14.9%) had occult cervical metastasis. The incidence of occult cervical metastasis of maxillary gingival SCC was higher than that of maxillary sinus SCC (17.1% and 12.5%, respectively). The 5-year overall survival rate was 51.9% for the END group and 74.0% for the non-END group. The success rate of treatment for regional recurrence was high at 71.4%, whereas that for local or locoregional recurrence was low (33.3% and 0%, respectively). Conclusion: The incidence of occult cervical metastasis of maxillary SCC was not high enough to recommend END. For survival of cN0 patients, local control of the primary tumor is more important than modality of neck management. Observation of cN0 neck is recommended when early detection of regional recurrence is possible irrespective of the site or T stage. The key enabler of early detection is patient education with periodic follow-up.

• Journal of Chest Surgery
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• 제39권1호
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• pp.1-11
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• 2006

배경: CD44는 세포상호간 그리고 세포와 기질 사이의 부착을 조절하는 세포표면당단백질로 표준형인 CD44s와 여러 동종변형이 있다. CD44는 림프구와 단핵구를 활성화할 뿐만 아니라, 여러가지 상피성 종양의 진행과정에 참여하여 종양의 침습과 전이를 도와줄 것이라는 연구결과가 나오고 있다. 그러나, 종양의 종류에 따라 CD44의 표준형과 여러 동종변형의 발현양상이 다르고, 종양의 생물학적 특성과의 관련성에 대해서도 아직은 잘 알려져 있지 않다. 폐장에는 많은 종류의 원발성 악성종양과 전이성종양이 발생하기 때문에 폐암조직에서 CD44 당단백의 발현양상에 대해 연구하는 것이 폐암의 생물학적 특성뿐만 아니라 다른 종양의 전이에 관한 이해의 폭을 넓히는데 도움이 될 것으로 생각하여 본 연구를 시행하였다. 대상 및 방법: 1985년부터 1994년까지 비소세포성폐암으로 진단한 후 절제하여 의뢰된 48예의 편평세포암종, 33예의 선암종, 8예의 미분화성대세포암종을 합한 총 89예의 폐암조직을 대상으로 연구하였다. CD44 당단백질은 표준형인 CD44s와 동종변형인 CD44v6에 대해 면역조직화학염색을 시행하여 발현정도를 평가하였다. 종양의 미세혈관분포는 혈관내피세포 표지자인 CD34에 대한 면역조직화학염색을 시행하여 200배 및 400배 현미경 시야에서 혈관의 수를 헤아렸다. CD44s와 CD44v6의 발현정도와 미세혈관의 수 사이에 연관성을 검정하였다. 이 결과를 환자의 나이, 성별, 병기, 종양의 크기, 림프절 전이 여부, 종양의 병리조직학적 유형 및 생존율과 비교하였다. 결과: CD44s와 CD44v6는 89예의 비소세포폐암종 중 각각 71예(79.8$\%$)와 64예(71.9$\%$)에서 발현하였다. 이 두 당단백의 발현은 상호 관련성이 있었다(p < 0.0001). CD44s와 CD44v6모두 편평세포암종에서 각각 95.8$\%$로 가장 높은 발현율을 보였다(p < 0.0001). CD44s의 발현은 편평세포암종의 분화도와 관련이 있었는데 (p=0.008), 불량한 분화를 보이는 암종이 양호한 분화의 암종보다 발현율이 높았으며(p=0.002), 중등도 분화를 보인 암종과는 유의한 차이가 없었다. CD44v6의 발현은 편평세포암종과 선암종의 분화도와 관련이 없었다. CD44s의 발현은 종양의 미세혈관의 수와 상관관계를 보였다(p=0.019 및 p=0.007). 종양의 미세혈관의 수는 종양의 크기와 상관 관계가 있었다 (각각 p=0.043). 그러나, 나이, 성별, 병기, 림프절 전이 및 생존율과는 관련성이 없었다. 결론: 이상의 결과에서, 종양의 미세혈관의 수가 CD44s의 발현과 상관관계가 있고, 종양의 크기와도 상관관계를 보이는 점으로 미루어 CD44s가 종양의 성장과 혈관 형성에 관련되어 있을 가능성을 시사한다. CD44s와 CD44v6의 발현이 편평세포암종에서 가장 높은 발현율을 보이는 것으로 보아 조직형태학적 특성과 관련이 있을 것으로 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1531-1537
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• 2014

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis.