Kuk Jin Choe

Predictors of operative morbidity and mortality in gastric cancer surgery

The aim of this study was to identify factors that predict morbidity and mortality in gastric cancer surgery.

Young age: an independent risk factor for disease-free survival in women with operable breast cancer

BackgroundThe incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients.MethodsWe retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups.ResultsA total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010).ConclusionYoung age (<35) is an independent risk factor for relapse in operable breast cancer patients.

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Methylation in the p53 promoter is a supplementary route to breast carcinogenesis : Correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma

Aberrant methylation in the CpG sites located in the promoter region of several tumor suppressor genes has been reported in various types of cancers. However, the methylation status of the p53 promoter has not been clearly determined and no information is available on its role in breast cancer. The aim of the study was to determine the presence and timing of the methylation of CpG sites in the p53 promoter, in the progression from ductal carcinoma in situ to invasive cancer. We also explored the correlation between the CpG methylation of the p53 promoter and p53 mutation during the progression of breast cancer. The corresponding lesions of both the invasive and noninvasive types were microdissected in paraffin-embedded tissue of 26 breast carcinomas. Bisulfite-modified DNA sequencing for methylation status in the p53 promoter was carried out, and double-strand DNA sequencing was performed in the promoter region and exons 4 to 9 of the p53 gene. CpG site methylation in the p53 promoter was detected in three cases (11.5%). Two noninvasive and three invasive lesions harbored CpG methylation in the p53 promoter. Methylations in more than one site were observed in three lesions, all of which contained methylation in two sites. The methylated CpG sites were located near the AP1 and YY-1 binding sites and at the YY-1 binding site. The p53 mutation was not found in the lesions where methylation in p53 promoter region was evident. In 16 cases (61.5%), neither methylation nor p53 mutation was detected. We conclude that the methylation in the p53 promoter region is found in the breast cancer irrespective of the status of invasion, and that the hypermethylation in the p53 promoter region is an alternative pathway to tumorigenesis where there is no p53 gene mutation.

Diagnostic Value of Positron Emission Tomography for Detecting Breast Cancer

Abstract. Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. PET has high sensitivity for detecting breast cancer, both the primary tumor and axillary node metastasis. From June 1995 to November 1996 a total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital. Whole-body PET images were obtained beginning 60 minutes after injection of 370 MBq (10 mCi) 18 F-fluorodeoxyglucose. Regional scans were also obtained with transmission images. We compared the PET results with those from the physical examination and mammography. All cases were histologically confirmed. The diagnostic accuracy of PET was excellent for the primary tumor mass (97%) compared with that of the physical examination (78%) and mammography (67%). For axillary lymph node metastasis, PET had outstanding detection accuracy (96%) compared with the physical examination and mammography (74% and 60%, respectively). Whole-body PET scans made it possible to see all of the metastatic lesions at a glance in cases of metastatic or recurrent breast cancer. There was a probable correlation between the standard uptake value (SUV) and the number of axillary lymph node metastases, but in this study statistical significance was not proved because of the small number of cases. PET also could detect breast cancer in paraffin-augmented breasts. We concluded that PET is a highly sensitive, accurate diagnostic tool for breast cancer and that SUV, after more studies, could be used as an important prognostic factor.

Fluorodeoxyglucose positron emission tomography for detection of recurrent or metastatic breast cancer

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging technique capable of identifying primary tumors and metastases with high sensitivity and accuracy. The aim of this study was to evaluate the diagnostic accuracy of whole-body FDG-PET imaging for the detection of recurrent or metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed on 27 patients with suspected recurrent breast carcinoma. PET images were evaluated qualitatively for each patient and lesion. FDG-PET scans showed that there were 61 reference sites of malignant or benign lesions in 27 patients. In a patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites with recurrent or metastatic disease and 11 of 13 without recurrence. The overall sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and 93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic lesions. In 13 patients treatment was altered by the outcome of the PET scan. We concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality for detecting recurrent or metastatic breast carcinoma in patients suspected of having recurrent disease after primary surgery.RésuméOn sait que le PET scan au FDG est une technique d’imagerie non-invasive capable d’identifier les tumeurs primitives et métastatiques avec une sensibilité et une précision élevées. Le but de cette étude a été d’évaluer la précision diagnostique du PET-FDG scan corps entier pour détecter une récidive ou des métastases du cancer du sein après intervention chirurgicale. Un PET-FDG scan corps entier a été réalisé chez 27 patientes suspectées d’avoir une récidive de cancer du sein. Les images ont été évaluées qualitativement pour chaque patiente et chaque lésion. L’analyse des images a montré 61 sites de lésions malignes ou bénignes chez ces 27 patientes. En ce qui concerne l’analyse individualisée par patiente, le PET-scan a correctement identifié 16 des 17 patientes ayant une récidive ou des métastases et 8 des 10 patientes sans récidives, pour une sensibilité, une spécificité et une précision respectivement de 94%, 80% et de 89%. En ce qui concerne l’analyse individualisée par lésions, le PET-FDG scan a correctement identifié 46 des 48 sites de récidives ou de métastases et 11 des 13 lésions sans métastases pour une sensibilité, une spécificité et une précision globales respectivement de 96%, 85% et de 93%. Le PET-FDG scan a révélé une récidive ou des métastases non suspectées chez 8 des 27 (30%) patientes et chez 11 des 20 (55%) patientes ayant déjà une métastase à distance. Le plan thérapeutique a été modifié par les résultats du PET scan chez 134 patientes. Nous concluons que le PET-FDG scan corps entier est utile pour la détection de récidives ou de métastases chez la patiente soupçonnée de récidive après chirurgie primitive pour cancer du sein.ResumenLa FDG-PET es una técnica no invasora de imágenes diagnósticas, capaz de identificar con alta sensibilidad y certeza tumores primarios y metástasis. El propósito del presente estudio fue evaluar la certeza diagnóstica de la imagenología de cuerpo entero por FDG-PET en la detección de carcinoma de seno recurrente o metastásico luego de tratamiento quirúrgico. La imagenología de cuerpo entero con FDG-PET se practicó en 27 pacientes con sospecha de carcinoma mamario recurrente. Las imágenes fueron evaluadas cualitativamente para cada paciente y cada lesión. Los estudios demonstraron 61 ubicaciones de lesiones malignas o benignas en 27 pacientes. En el análisis basado en el paciente, los estudios con FDG-PET identificaron correctamente 16 de 17 pacientes con enfermedad recurrente o metastásica y 8 de 10 libres de recurrencia. lo cual significó sensibilidad, especificidad y certeza de 94%, 80% y 89%, respectivamente. En el análisis basado en la lesión, las imágenes identificaron correctamente 46 de 48 ubicaciones de lesiones, con enfermedad recurrente o metastásica de 11 y 13 libres de recurrencia. Las tasas globales de sensibilidad, la especificidad y la certeza para todas las ubicaciones fueron 96%, 85% y 93%, respectivamente. Los estudios con FDG-PET revelaron enfermedad recurrente o metastásica no sospechada en 8 de 27 (30%) pacientes y lesiones metastásicas distantes en 11 de 20 (55%). En 13 pacientes se modificó el tratamiento como resultado del estudio por PET. Nuestra conclusión es que la escanografía de cuerpo entero por FDG-PET es una modalidad de imagenología diagnóstica útil en la detección de carcinoma recurrente o metastásico en pacientes con sospecha de enfermedad recurrente luego de tratamiento quirúrgico primario.

Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk

The estrogen receptor-alpha (ERalpha) has been known to play a role in the development and progression of breast cancer. Several genetic polymorphisms in the ERalpha gene have been related to breast cancer risk and/or different tumor characteristics. In this study, PCR and direct sequencing based methods were used to examine this issue further in a Korean study population consisting of 155 women, 110 with breast cancer and 45 without cancer. We also assessed the potential role of the ERalpha genotype in ER, PR, p53, c-erbB2, and bcl-2 expression. Only one of the allelic variants of ERalpha gene was found in our study subjects; the (C(975)G) change was present in half of the study subjects. Although this allele had no direct effect in individual breast cancer risk, it was positively associated with tumor PR (P for trend=0.04) and ER expression (P for trend=0.06) and negatively associated with p53 expression (P for trend=0.02).

Prognostic significance of Bcl-2 and p53 expression in gastric cancer

Background and aimsApoptosis regulates cell death and influences cell proliferation and therefore may play an important role in development or growth of various malignant tumors. The Bcl-2 and p53 are closely linked in the regulation of apoptosis. We investigated the prognostic significance of Bcl-2 and p53 expression in patients with gastric cancer.Patients and methodsImmunohistochemistry was used to study Bcl-2 and p53 expression in 308 consecutive patients with gastric cancer.ResultsBcl-2 expression was positive in 39 patients (12.7%) and showed a significant negative correlation with depth of invasion and lymph node metastasis. p53 expression was observed in 105 patients (34.1%) and was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and intestinal type. Patients with Bcl-2+ tumors showed a trend to better 5-year survival rate (81%) than those with Bcl-2− negative tumors (71%). The 5-year survival rate in p53 positive cases (60%) was significantly lower than that in p53-negative cases (78%). In addition, p53 expression showed a significantly poorer prognosis in both diffuse and intestinal types. In multivariate analysis restricted to patients with R0 resection p53 expression was an independent prognostic factor (relative risk: 2.063). In combined assessment of p53 and Bcl-2 expression the group with p53+/Bcl-2− tumors showed significantly worse 5-year survival (57%) than the other groups, while best survival was seen in the group with p53+/Bcl-2+ tumors (100%).Conclusionp53 expression is an unfavorable prognostic factor in gastric cancer. Bcl-2 expression may have possible prognostic value when combined with p53 expression.

Intraoperative gastroscopy for gastric surgery.

Background:Few reports are available on the use of intraoperative gastroscopy for gastric surgery.Methods:The details of 33 patients (25 early gastric cancers and eight gastric submucosal tumors) who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. The type of operation or resection margin was determined by evaluating both sides of the stomach simultaneously by combined operative and gastroscopic methods.Results:Preoperative endoscopic clipping was done preferentially for early gastric cancer. However, when precise localization was needed, intraoperative gastroscopy was used. Curative gastric resection was possible in 25 early gastric cancer patients after accurate lesion localization. Laparoscopic wedge resections of submucosal tumors were performed in seven patients without stenosis by combined laparoscopic and gastroscopic methods.Conclusions:Intraoperative gastroscopy can be used effectively during gastric surgery for early gastric cancer or submucosal tumors and can be regarded as a modern stethoscope to gastric surgeons.

Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk

We conducted a hospital-based case–control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P ≤ 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.