Prognostic significance of cyclooxygenase-2 expression in invasive breast carcinoma

의학과/석사[한글] 배경: Cyclooxygenase(COX-1, COX-2)는 arachidonic acid를prostaglandin으로 전환시키는 주요 효소이다. COX-2는 성장인자, 발암유전자, 발암물질과 cytokine 등의 자극에 의해서 발현되어 악성 종양의 성장, 침윤 및 전이 등 전반에 걸쳐 관여 한다고 알려지고 있다. 저자들은 침윤성 유방암에서의 COX-2의 발현과 기존의 알려진 여러 임상 병리학적 인자들과의 상관성을 조사하고 유방암 환자들의 무병생존율 및 전체 생존율의 예후 인자로서의 효용성을 알아보고자 하였다. 대상 및 방법: 침윤성 유방암으로 수술 받은 293명의 환자들의 종양 조직을 조직미세배열과 면역조직화학염색을 통하여 COX-2 발현도를 조사하였다.결과: 전체 293예 중 116예(39.59%)에서 COX-2 양성으로 관찰되었으며, 유방암의 임상 및 병리학적 인자들과의 상관성 조사에서는 조직학적 등급(p=0.004), 호르몬 수용체의 음성도(ER:p=0.002 / PgR:p=0.024)와 통계적으로 유의성 있게 나타났다.그러나, 진단 당시의 나이, 종양의 크기, 액와부 림프절의 전이상태, 광범위 관내암종성분, 종양주위의 림프혈관침윤, HER-2/neu 증폭, 무병생존율, 전체생존율과는 통계적 유의성은 없었다. 하위그룹 분석에서는 에스트로겐 수용체 양성인 그룹에서 COX-2발현이 생존율에 더욱 나쁜 영향을 주는 것으로 조사되었다. 결론: 본 연구결과에서 COX-2발현이 불량한 예후를 가지는 유방암에서 더욱 흔하게 나타나는 것으로 관찰되었다. 그러나, COX-2 발현과 유방암 환자의 예후와의 관계를 확실히 정립하기 위해서는 더욱 광범위한 연구가 필요하리라 사료된다 [영문]Background: Cyclooxygenase 1 and 2(COX-1 and COX-2) are key enzymes that convert arachidonic acid to prostaglandins. COX-2 is induced by responding to growth factors, inflammatory mediators, cytokines, tumor promoters, and oncogenes. COX-2 plays a role in malignant tumor development and progression. We investigated the prognostic impact of expression of COX-2, on disease-free survival and overall survival in patients with invasive breast carcinoma as well as the association between COX-2 expression and other clinicopathologic parameters.Material and Methods: We analyzed the expression of COX-2 protein by immunohistochemistry in tissue microarray specimens of 293 invasive breast carcinoma.Results: Expression of COX-2 was observed in 39.6% of the tumors, and it was associated significantly with histologic grade(p=0.004), negative estrogen receptor status(p=0.002) and negative progesterone receptor status(p=0.024). In contrast, there was no stastistically significant correlation with age, tumor size, nodal status, extensive intraductal component, lymphovascular invasion, HER-2 amplification, disease-free survival and overall survival. Interestingly, association with unfavorable disease-free survival and unfavorable overall survival was apparent in the subgroup defined by estrogen receptor positivity(p<0.0001, p=0.0002 respectively).Conclusions: These results suggest that COX-2 expression is more common associated with poor prognostic factors. But, further studies with larger series of patients are necessary to confirm the association and to evaluate the subgroup of estrogen receptor positive patients.ope

Predicting the Status of the Nonsentinel Lymph Nodes in early Breast Cancer Patients with Positive Sentinel Lymph Nodes

Purpose: The need for completion axillary lymph node dissection, even in early breast cancer patients with a positive sentinel lymph node, has been questioned. The purpose of this study was to determine the factors that predict the presence of metastasis in non-sentinel lymph nodes (NSLNs) when the sentinel lymph node (SLN) was positive. Methods: Between December 1998 and June 2004, the records of 104 early breast cancer patients with a positive SLN and who underwent completion axillary lymph node dissection were reviewed. The clinicopathological features in SLN-positive patients were evaluated as possible predictors of metastatic NSLN. Results: Forty four (42.3%) of the 104 patients with positive SLN had metastatic NSLNs. In a univariate analysis, unicentric multifocality (P=0.016), lymphovascular invasion (P=0.006) and SLN metastasis larger than 2 mm (P= 0.003) were associated with positive NSLN findings. The number of SLNs removed was significantly associated as a negative predictor (P=0.043). A multivariate analysis revealed that SLN metastasis ＞2 mm (P=0.021) and lymphovascular invasion (P=0.040) were independent predictors of metastatic NSLN. Conclusion: The likelihood of metastatic NSLNs correlates with the size of the largest SLN metastasis and the presence of lymphovascular invasion of the primary tumor. Even though in early breast cancer with positive SLNs, incorporating these factors may help determining which patients would benefit from additional axillary lymph node dissection.ope

Intraoperative Examination of Sentinel Lymph Nodes Using Rapid Cytokeratin Immunohistochemical Staining in Breast Cancer Patients

Purpose: Sentinel lymph node (SLN) biopsy has become a new standard procedure in the treatment of patients with early breast cancer. Furthermore, many institutions have begun offering the sentinel lymph node biopsy without simultaneous axillary dissection as a possible standard procedure when the SLN was free from tumors. For appropriate intraoperative decision making on the presence of cancer cells in axillary lymph nodes, a fast and accurate method to assess the SLN is required. The authors performed a prospective investigation of the relative merits of rapid cytokeratin immunohistochemical (IHC) staining of the SLN removed during the operations of breast cancer patients. Methods: Between December 2002 and August 2003, 38 patients with T1and T2 breast cancer were enrolled after undergoing successful sentinel lymph node biopsy. A total of 60 sentinel lymph nodes (mean number, 1.58) were biopsied and first examined by hematoxylin-eosin (H&E) staining. All the tumor free sentinel lymph nodes by H&E stained section were immunostained for cytokeratin using a rapid immunohistochemical assay (Cytokeratin (PAN), 1：50,Newcastle, UK) during the operation. Finally, the sentinel lymph nodes were submitted for paraffin embedding and serial section after surgery. Both H&E stained and cytokeratin immunostained sections were also performed. Results: This technique has a turnaround time of less than 20 minutes during the operation. Rapid IHC staining revealed 4 positive sentinel lymph nodes that were negative for metastasis by H&E staining. Among these false negative 4 cases, two cases had problems with the frozen section of H&E staining and the other 2 cases had problems due to micrometastasis. This study showed a sensitivity of 88.89%, a specificity of 100%, an accuracy of 98.33%, and a negative predictive value of 98.08%. The false-negative case (1 of 52), which was negative on H&E staining and rapid IHC staining during the operation, was disclosed as positive only after a serial permanent section examination with IHC stain. Conclusion: The introperative examination of sentinel lymph nodes is a highly accurate and effective way of predicting the axillary lymph node status of patients with breast cancers. This may be a promising technique in deciding whether to spare axillary lymph node dissection for the patient in the operating roomope

Pegteograstim prophylaxis for chemotherapy-induced neutropenia and febrile neutropenia: a prospective, observational, postmarketing surveillance study in Korea

The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases