- Email: [email protected]
P027 The analysis of cytogenetic intra-tumoral heterogeneity in squamous cell carcinoma of the breast
14th St.Gallen International Breast Cancer Conference / The Breast 24S1 (2015) S26–S86
S35
P026 Mechanical ventilation promotes lung metastasis in 4T1 breast cancer lung-metastasized models
P027 The analysis of cytogenetic intra-tumoral heterogeneity in squamous cell carcinoma of the breast
Y. Huang1 *, L. Pan2 , K. Helou3 , Q. Xia2 , T. Zhao2 , H.-Y. Li2 , B. Xu2 , J. Zhang3 , Z. Chen2 , H. Li2 . 1 Breast Cancer Department, Sodra Alvsborgs Sjukhus, Boras, Sweden, 2 China–Japan Friendship Hospital, Beijing, China, 3 Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden
M. Oikawa1 *, A. Igawa2 , M. Ishida1 , Y. Nakamura1 , S. Nishimura1 , C. Koga1 , S. Akiyoshi1 , Y. Koi1 , K. Taguchi2 , S. Ohno1 . 1 Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 2 Pathology, National Kyushu Cancer Center, Fukuoka, Japan
Goals: Recent evidence suggests that general anaesthesia and perioperative factors significantly increased risk of cancer recurrence compared to locoregional anaesthesia in patients undergoing surgery, however, their effects on behavior of cancer cells are not yet known. The endothelial cell and epithelial disruption was observed during mechanical ventilation, general anaesthesia in animal models. This study was to test the hypothesis that mechanical ventilation during cancer surgery induces lung stroma/tissue milieu changes, creating a favorable microenvironment for postoperative lung metastatic tumor establishment. Methods: Female BALB/c mice were anesthetized by intraperitoneal pentobarbital administration and divided into a mechanical ventilation group [mice ventilated with low pressures and low tidal volumes, 60 min; n = 8) and a control group (no ventilation; n = 8). All the mice were subjected to intravenous injection of murine mammary adenocarcinoma 4T1-green fluorescent protein (GFP) 105 cells during anaesthesia. 24 hr later, sections from the lung tissue were examined and 4T1 celler were counted by direct GFP fluorescence observation, hematoxylineosin histology and Ep-CAM immunohistochemistry. To closely mimic human cancer surgical and anaesthetic manipulation, A clinically relevant animal model of spontaneous breast cancer lung metastasis with surgical resection of primary tumor was used to investigate the purified mechanical ventilation event that dictate lung metastasis post-operation. Female BALB/c mice were inoculated with metastatic murine mammary adenocarcinoma 4T1 cells in the mammary fat pad (3×105 /mouse). After 14 day growth, mice were anesthetized by intraperitoneal pentobarbital administration and divided into a mechanical ventilation group [mice ventilated with low pressures and low tidal volumes, 60 min; n = 6) and a control group (no ventilation; n = 6). All the mice were subjected to flank tumor resection during anaesthesia. Two weeks later, Metastatic tumor burden was assessed by both macroscopic metastatic nodule count and hematoxylin-eosin histology. Results: Mechanical ventilation was associated with increased circulating breast tumor cells arrest at microvasculature of lung (P = 0.01). The histology analysis data indicated that mechanical ventilation induced endothelial-epithelium abnormalities, inflammatory reaction and significantly upregulated the expression of epithelial adhesion molecules (Ep-CAM). Postoperative metastases exhibited significantly increase in mechanical ventilated groups in comparison with those in non-ventilated group (P < 0.05). Conclusion: Mechanical ventilation led to a progressive phenotype of lung metastases that exhibited a microenvironment for cancer cell adhesion, invasion, survive and growth within lungs. Disclosure of Interest: No significant relationships.
Goals: Squamous cell carcinoma (SCC) of the breast is rare and generally aggressive disease constituting less than 0.1% of all breast carcinomas. Albeit their distinctive morphological feature, the origin and cytogenetic profile of SCC are still not well understood. In this study, three cases of SCC of the breast which consists of SCC component and invasive or noninvasive ductal carcinoma of no special type (NST) component were analyzed to elucidate the cytogenetic intra-tumoral heterogeneity and the origin of SCC of the breast. Methods: Among pathologigal database for 3,000 patients with breast cancer, five patients with SCC were determined. Their medical records were retrospectively reviewed to obtain clinicopathological, radiological, treatment and outcome information. Among them, three cases showed morphological intra-tumoral heterogeneity, thus components of SCC and invasive or noninvasive ductal carcinoma of NST were contained. Both components of each case were separately macro-dissected using five 10-mm-thick sections and tumor DNA was extracted using the QIAmp DNA Mini Kit (Qiagen), followed by array comparative genomic hybridization (aCGH) analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8×60k microarray). The cytogenetic profile of SCC component was compared with paired NST component in each case. Results: Sufficient amounts of DNA were obtained with an average of 0.79 mg (0.54–1.04 mg). The quality of the aCGH was acceptable, as judged by the mean derivative log ratio spread (DLRSpread) of 0.475 (0.36–0.55), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes. The cytogenetic profiles of SCC and NST component were almost identical in case 2 and case 3. However comparing with NST component, large number of copy number aberrant (CNA) region was detected in SCC component and all aberration in NST component were encompassed in SCC component in case 1. There is no common SCC component specific aberration in the three cases. Conclusion: Our result showed diversity of cytogenetic intratumoral heterogeneity in SCC of breast. Comparison with cytogenetic profile in one case indicated that the SCC component originated from NST component. Disclosure of Interest: No significant relationships. P028 Characteristics of mucocele-like tumors K. Takebe *, T. Arai. Breast Surgery, Takebe Breast Cancer Care Clinic, Takamatsu, Japan Goals: Mucocele-like tumors (MLT) are mucus-producing benign lesions that have been proposed by Rosen. Since the malignant merger case exists, attention to diagnosis and treatment is needed. The purpose of this study is the elucidation of the pathological diagnosis and image diagnosis of MLT and the construction of the treatment strategy. Methods: From 1997 to 2013, 70 cases of MLT were diagnosed in our facility. Excisional biopsy (or lumpectomy) accounted for 35 cases. In the 2008–2013 period, we examined 35 follow-up cases of MLT without ductal hyperplasia that were diagnosed by fine-needle aspiration cytology (FNAC) or core needle biopsy (CNB).
S35
P026 Mechanical ventilation promotes lung metastasis in 4T1 breast cancer lung-metastasized models
P027 The analysis of cytogenetic intra-tumoral heterogeneity in squamous cell carcinoma of the breast
Y. Huang1 *, L. Pan2 , K. Helou3 , Q. Xia2 , T. Zhao2 , H.-Y. Li2 , B. Xu2 , J. Zhang3 , Z. Chen2 , H. Li2 . 1 Breast Cancer Department, Sodra Alvsborgs Sjukhus, Boras, Sweden, 2 China–Japan Friendship Hospital, Beijing, China, 3 Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden
M. Oikawa1 *, A. Igawa2 , M. Ishida1 , Y. Nakamura1 , S. Nishimura1 , C. Koga1 , S. Akiyoshi1 , Y. Koi1 , K. Taguchi2 , S. Ohno1 . 1 Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 2 Pathology, National Kyushu Cancer Center, Fukuoka, Japan
Goals: Recent evidence suggests that general anaesthesia and perioperative factors significantly increased risk of cancer recurrence compared to locoregional anaesthesia in patients undergoing surgery, however, their effects on behavior of cancer cells are not yet known. The endothelial cell and epithelial disruption was observed during mechanical ventilation, general anaesthesia in animal models. This study was to test the hypothesis that mechanical ventilation during cancer surgery induces lung stroma/tissue milieu changes, creating a favorable microenvironment for postoperative lung metastatic tumor establishment. Methods: Female BALB/c mice were anesthetized by intraperitoneal pentobarbital administration and divided into a mechanical ventilation group [mice ventilated with low pressures and low tidal volumes, 60 min; n = 8) and a control group (no ventilation; n = 8). All the mice were subjected to intravenous injection of murine mammary adenocarcinoma 4T1-green fluorescent protein (GFP) 105 cells during anaesthesia. 24 hr later, sections from the lung tissue were examined and 4T1 celler were counted by direct GFP fluorescence observation, hematoxylineosin histology and Ep-CAM immunohistochemistry. To closely mimic human cancer surgical and anaesthetic manipulation, A clinically relevant animal model of spontaneous breast cancer lung metastasis with surgical resection of primary tumor was used to investigate the purified mechanical ventilation event that dictate lung metastasis post-operation. Female BALB/c mice were inoculated with metastatic murine mammary adenocarcinoma 4T1 cells in the mammary fat pad (3×105 /mouse). After 14 day growth, mice were anesthetized by intraperitoneal pentobarbital administration and divided into a mechanical ventilation group [mice ventilated with low pressures and low tidal volumes, 60 min; n = 6) and a control group (no ventilation; n = 6). All the mice were subjected to flank tumor resection during anaesthesia. Two weeks later, Metastatic tumor burden was assessed by both macroscopic metastatic nodule count and hematoxylin-eosin histology. Results: Mechanical ventilation was associated with increased circulating breast tumor cells arrest at microvasculature of lung (P = 0.01). The histology analysis data indicated that mechanical ventilation induced endothelial-epithelium abnormalities, inflammatory reaction and significantly upregulated the expression of epithelial adhesion molecules (Ep-CAM). Postoperative metastases exhibited significantly increase in mechanical ventilated groups in comparison with those in non-ventilated group (P < 0.05). Conclusion: Mechanical ventilation led to a progressive phenotype of lung metastases that exhibited a microenvironment for cancer cell adhesion, invasion, survive and growth within lungs. Disclosure of Interest: No significant relationships.
Goals: Squamous cell carcinoma (SCC) of the breast is rare and generally aggressive disease constituting less than 0.1% of all breast carcinomas. Albeit their distinctive morphological feature, the origin and cytogenetic profile of SCC are still not well understood. In this study, three cases of SCC of the breast which consists of SCC component and invasive or noninvasive ductal carcinoma of no special type (NST) component were analyzed to elucidate the cytogenetic intra-tumoral heterogeneity and the origin of SCC of the breast. Methods: Among pathologigal database for 3,000 patients with breast cancer, five patients with SCC were determined. Their medical records were retrospectively reviewed to obtain clinicopathological, radiological, treatment and outcome information. Among them, three cases showed morphological intra-tumoral heterogeneity, thus components of SCC and invasive or noninvasive ductal carcinoma of NST were contained. Both components of each case were separately macro-dissected using five 10-mm-thick sections and tumor DNA was extracted using the QIAmp DNA Mini Kit (Qiagen), followed by array comparative genomic hybridization (aCGH) analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8×60k microarray). The cytogenetic profile of SCC component was compared with paired NST component in each case. Results: Sufficient amounts of DNA were obtained with an average of 0.79 mg (0.54–1.04 mg). The quality of the aCGH was acceptable, as judged by the mean derivative log ratio spread (DLRSpread) of 0.475 (0.36–0.55), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes. The cytogenetic profiles of SCC and NST component were almost identical in case 2 and case 3. However comparing with NST component, large number of copy number aberrant (CNA) region was detected in SCC component and all aberration in NST component were encompassed in SCC component in case 1. There is no common SCC component specific aberration in the three cases. Conclusion: Our result showed diversity of cytogenetic intratumoral heterogeneity in SCC of breast. Comparison with cytogenetic profile in one case indicated that the SCC component originated from NST component. Disclosure of Interest: No significant relationships. P028 Characteristics of mucocele-like tumors K. Takebe *, T. Arai. Breast Surgery, Takebe Breast Cancer Care Clinic, Takamatsu, Japan Goals: Mucocele-like tumors (MLT) are mucus-producing benign lesions that have been proposed by Rosen. Since the malignant merger case exists, attention to diagnosis and treatment is needed. The purpose of this study is the elucidation of the pathological diagnosis and image diagnosis of MLT and the construction of the treatment strategy. Methods: From 1997 to 2013, 70 cases of MLT were diagnosed in our facility. Excisional biopsy (or lumpectomy) accounted for 35 cases. In the 2008–2013 period, we examined 35 follow-up cases of MLT without ductal hyperplasia that were diagnosed by fine-needle aspiration cytology (FNAC) or core needle biopsy (CNB).