• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5539-5544
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• 2014

Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype.

• Journal of Life Science
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• v.20 no.4
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• pp.528-534
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• 2010

Garlic (Allium sativum) has been well-known as a folk remedy for a variety of ailments since ancient times, and it is well documented that enhanced garlic consumption leads to a decrease in incidences of cancer. Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, we investigated the potential effects of water extract of aged black garlic (ABG) on the correlation between tightening of TJs and anti-invasive activity in human gastric carcinoma AGS cells. The inhibitory effects of ABG on cell motility and invasiveness were found to be associated with increased tightness of TJs, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, the activities of MMP-2 and -9 in AGS cells were inhibited by treatment with ABG, and this was also correlated with a decrease in the expression of their mRNA and proteins. Furthermore, RT-PCR and immunoblotting results indicated that ABG repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. In conclusion, these results suggest that ABG treatment may inhibit tumor metastasis and invasion, and therefore may act as a dietary source to decrease the risk of developing cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.2
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• pp.105-115
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• 2005

Purpose: The lymph node status assessed by conventional histological examination is the most important prognostic factor in patients undergoing surgery for oral squamous cell carcinoma. The presence of lymph node metastasis has a strong adverse impact on patient survival even after extended radical resection. Despite these findings, tumour recurrence is not rare after surgery, even when histological examination shows no lymph node metastasis. Recently, molecular-genetically and immunohistochemically demonstrated micrometastasis to the lymph nodes has been shown to have a significant adverse influence on survival in patients with squamous cell carcinoma and histologically negative nodes. The present study sought to determine the incidence and clarify the clinical significance of molecular-genetically and immunohistochemically demonstrated nodal micrometastases and to correlate these data with the stage of oral cancer. Methods: Lymph nodes systematically removed from 71 patients who underwent curative resection between 1998 and 2003 with head and neck squamous cell carcinoma were examined molecular-genetically to detect cytokeratin 5 mRNA with RT-PCR and immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes. Results: micrometastases were detected in 43(60%) of 71 patients by RT-PCR and 26(36%) of 71 patients by immunohistochemistry. By RT-PCR analysis, patients exhibiting a positive band for CK 5 mRNA had a significantly worse prognosis than those were RT-PCR negative. By immunohistochemistry, the presence of micrometastasis did not predict patient outcome. Conclusion: Micrometastases detected by RT-PCR may be of clinical value in identifying patients who may be at high risk for recurrence and who are therefore likely to benefit from systemic adjuvant therapy.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.104-110
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• 2009

Purpose: Compared to soft tissue sarcoma, the relative risk of extraskeletal osteosarcoma is still not clear. The purpose of this study is to identify the difference in survival and local recurrence rate between two soft tissue sarcomas. Materials and Methods: Twelve patients with pathologically confirmed extraskeletal osteosarcoma were analysed. For retrospective matched case-control study, we selected 72 patients who were confirmed as high grade soft tissue sarcoma and had similar tumor location, tumor size and age to extraskeletal osteosarcoma. Results: Median age was 50 years old. Five cases were located in upper extremity, four in the buttocks, three in the lower extremity. Overall survival rate of extraskeletal osteosarcoma group and high grade soft tissue sarcoma group at 5 years were 52% and 55%. There is no significant difference (p=0.8). Local recurrence rate and metastasis rate were 58%, 67% in extraskeletal osteosarcoma group and 36%, 51% in soft tissue sarcoma group, which were not stastistically significant(p=0.2, p=0.4). Conclusion: Extraskeletal osteosarcoma have similar local recurrence, metastasis and survival rate compare to high grade soft tissue sarcoma. The number of patients of this study were too small to identify outcome of extraskeletal osteosarcoma. Further multi-institutional study should be attempted.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.173-181
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• 2012

Purpose: To evaluate the prognostic value of preoperative neck lymph node (LN) assessment with $^{18}F$-fluorodeoxyglucose positron emission tomography ($^{18}F$-FDG PET), computed tomography (CT), and magnetic resonance imaging (MRI) in oral cavity squamous cell carcinoma (OSCC) patients with pathologically positive LN. Materials and Methods: In total, 47 OSCC patients with pathologically positive LN were retrospectively reviewed with preoperative $^{18}F$-FDG PET and CT/MRI. All patients underwent surgical resection, neck dissection and postoperative adjuvant radiotherapy and/or chemotherapy between March 2002 and October 2010. Histologic correlation was performed for findings of $^{18}F$-FDG PET and CT/MRI. Results: Thirty-six (76.6%) of 47 cases were correctly diagnosed with neck LN metastasis by $^{18}F$-FDG PET and 32 (68.1%) of 47 cases were correctly diagnosed by CT/MRI. Follow-up ranged from 20 to 114 months (median, 56 months). Clinically negative nodal status evaluated by $^{18}F$-FDG PET or CT/MRI revealed a trend toward better clinical outcomes in terms of overall survival, disease-free survival, local recurrence-free survival, regional nodal recurrence-free survival, and distant metastasis-free survival rates even though the trends were not statistically significant. However, there was no impact of neck node standardized uptake value ($SUV_{max}$) on clinical outcomes. Notably, $SUV_{max}$ showed significant correlation with tumor size in LN (p < 0.01, $R^2$ = 0.62). PET and CT/MRI status of LN also had significant correlation with the size of intranodal tumor deposit (p < 0.05, $R^2$ = 0.37 and p < 0.01, $R^2$ = 0.48, respectively). Conclusion: $^{18}F$-FDG PET and CT/MRI at the neck LNs might improve risk stratification in OSCC patients with pathologically positive neck LN in this study, even without significant prognostic value of $SUV_{max}$.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2947-2951
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• 2015

Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the $BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between $BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including $BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. $BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was $0.33{\pm}0.21cm$. The $BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.43-45
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• 2013

Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population. Materials and Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM. Results: The left to right sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The right sided BC was observed in younger age group (46:52 years; p<0.0001) and with a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM had relatively higher negative receptor status with a significant predominance of right sided BC. The overall incidence of BM on BS was 28% and relatively higher in right than left breast (33%:24% p=0.068). The average number of BM sites was also significantly greater for the right side (6:4, P<0.0001). The % cumulative risk of BM in right breast was noted at significantly smaller PTS than left side with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event free survival of BM in left sided BC was significantly higher than for the right side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right BC. Conclusions: 1) A left sided predominance of BC was seen in local population; 2) right sided BC had a more aggressive behavior with extensive and earlier appearance of BM at relatively younger age, smaller PTS and receptor (s) negativity.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.169-175
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• 2004

Purpose: The tumor suppressor gene p53 has been shown to be a factor in the carcinogenesis or progression of gastric cancer. The mutant p53 has been reported to cause a higher risk of lymph-node metastasis. Futhermore, mutation of the p53 has been linked to a poor prognosis for gastric cancer. The heat shock protein-27 (HSP27), a stress protein, has also been reported to be a poor prognostic factor in ovarian and breast cancers. However, in gastric-cancer patients, controversies exist as to its influence on the prognosis. In the present study, we used an immunohistochemical stain to observe the effects of p53 and HSP27 on the clinicopathological factors and on the prognosis for gastric-cancer patients. Materials and Methods: To evaluate the significance of p53 and HSP27 in gastric cancer patients, we analyzed 212 cases of gastric cancer (stage I.IV). Tissue samples of 212 patients were stained immunohistochemically for the mutant p53 protein and for HSP27. The correlations between protein expression and the clinicopathological factors were investigated. Results: The overall expression rates for p53 and HSP27 were $36.9\%\;and\;27.8\%$, respectively. p53 and HSP27 were correlated to each other because the HSP27 expression rate was higher in the p53-positive group (P=0.046). Statistically, the p53 and the HSP27 expression rates were significantly increased in the case of tumor invasiveness, lymphatic metastasis and vessel involvement. Therefore, they play a role in cancer progression. The 5-year survival rates of the p53-positive and the p53-negative groups were $62.8\%\;and\;60.1\%$, respectively (P=0.793) while the 5-year survival rates for the HSP27-positive and HSP27-negative groups were $54.2\%\;and\;63.1\%$, respectively (P=0.090). Conclusion: p53 and HSP27 were correlated to each other in our immunohistochemical study of gastric carcinomas and they were not independent prognostic factors in gastric- cancer patients. However, further studies are needed to determine their prognostic values for gastric-cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.27-32
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• 2009

Background: The management of patients with lung cancer has improved recently, and many of them will require admission to the medical intensive care unit (MICU). The aim of this study was to examine the clinical characteristics and to identify risk factors for mortality in patients with lung cancer admitted to the MICU. Methods: We conducted retrospective analysis on 88 patients with lung cancer admitted to the MICU between April 2004 and March 2008. Results: Of the 88 patients (mean age, 66 years), 71 patients (80.7%) had non-small cell lung cancer and 17 patients (19.3%) had small cell lung cancer. Distant metastasis were present in 79 patients (89.8%). The main reasons for MICU admission were acute respiratory failure (77.3%), sepsis (11.4%), and central nervous system dysfunction (4.5%). Mechanical ventilation was used in 54 patients (61.4%). Acute Physiology and Chronic Health Evaluation (APACHE) II score, length of MICU stay, need for mechanical ventilation, source of MICU admission were correlated with MICU mortality. The type of lung cancer and metastasis were not predictive factors of death in MICU. Conclusion: Most common reason for ICU admission was acute respiratory failure. Mortality rate of lung cancer patients admitted to the MICU was 65.9%. APACHE II score, length of ICU stay, need for mechanical ventilation, source of MICU admission were predicted factors of death in the MICU.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3319-3322
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• 2013

Background: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown. Materials and Methods: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated. Results: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes. Conclusions: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.