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      POU5F1/Oct-4 expression in breast cancer tissue is significantly associated with non-sentinel lymph node metastasis

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          Abstract

          Background

          At present, few studies have explored the significance of POU5F1 (also known as octamer-bingding factor, Oct-4 or Oct-3) expression in breast cancer tissues.

          Methods

          A total of 121 patients were retrospectively selected between May 2010 and March 2013 to investigate the relationship between POU5F1/Oct-4 expression in breast cancer tissues and non-sentinel lymph node (non-SLN) metastases and to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. All patients had early-stage breast cancer, which was histologically confirmed by the Department of Surgical Oncology, The First Affiliated Hospital of China Medical University. Histological type and grade of tumors were determined from tissue samples by hematoxylin and eosin staining, while the presence of POU5F1 /Oct-4 protein was determined by immunohistochemistry. POU5F1/Oct-4 expression levels in tissues obtained from patients with sentinel lymph node (SLN) and non-SLN metastasis and in tissues obtained from patients without lymph node metastases were compared.

          Results

          POU5F1 /Oct-4 expression levels in breast cancer tissues were significantly higher in both the SLN metastasis and non-SLN metastasis groups ( P = 0.003 and P = 0.030, respectively). Furthermore, POU5F1/Oct-4 expression was found to be associated to both histological ( P = 0.01) and molecular type ( P = 0.03). Thus, our data once again confirms the validity of the MSKCC nomogram. The area under curve (AUC) was 0.919 (95 % CI: 0.869–0.969, P < 0.001). The probability of non-SLN metastasis generated from the MSKCC nomgram was significantly higher in the POU5F1 /Oct-4 positive group than in the POU5F1/Oct-4 negative group. Both univariate and multivariate analysis revealed that Oct-4 expression levels were significantly associated with non-SLN metastases ( P = 0.030 and P = 0.034, respectively).

          Conclusions

          POU5F1 /Oct-4 expression levels are significantly associated with non-SLN metastases. Patients with higher probabilities of metastasis generated from the MSKCC nomogram may also have higher POU5F1/Oct-4 expression levels.

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          Most cited references17

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          Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases.

          Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.
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            Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells.

            The totipotent stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this element is specifically active in embryonic stem and embryonic germ cells. The proximal element directs the epiblast-specific expression pattern, including downregulation during gastrulation; in cell lines its activity is restricted to epiblast-derived cells. Thus, Oct-4 expression in the germline is regulated separately from epiblast expression. This provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the totipotent cycle is dependent on a set of factors unique to the germline.
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              Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe.

              We have recently reported on a technique of gamma probe localization of radiolabelled lymph nodes to identify the sentinel node in malignant melanoma. In order to determine whether this technique is applicable to assist in staging breast cancer, a pilot study was begun to address two questions: (i) can the sentinel lymph node draining a breast cancer be identified for selective resection; and (ii) is the sentinel lymph node predictive of the status of the entire axillary lymph nodes? One to four hours prior to axillary lymph node dissection, 22 consecutive patients had approximately 0.4 mCi of technetium sulfur colloid in 0.5 ml saline injected around the perimeter of the breast lesion. A hand-held gamma counter was used at surgery to locate the lymph node(s) receiving drainage from the breast. A sentinel lymph node was identified in 18 of 22 patients. Of these 18 patients, the sentinel lymph node was positive in seven of seven patients, with pathologically verified metastatic breast cancer to at least one lymph node. In three out of seven patients, the sentinel lymph node was the only lymph node with metastatic cancer. In this pilot study of breast cancer patients, we conclude that: (i) radiolocalization and selective resection of sentinel lymph nodes is possible; and (ii) the sentinel lymph node appears to predict correctly the status of the remaining axilla. These data justify a larger clinical trial to verify the value of this technique.
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                Author and article information

                Contributors
                niccsl@163.com
                niccslgjt@163.com
                Jinfeng66cn@hotmail.com
                Liu_jisheng@hotmail.com
                AGZYQC@163.com
                chbyxl@163.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                1 March 2016
                1 March 2016
                2016
                : 16
                : 175
                Affiliations
                [ ]Department of Breast Surgery, The First Hospital of China Medical University, #155, Nanjingbei Street, Heping District, Shenyang, Liaoning Province PR China
                [ ]Department of Surgery, Ansteel Group Hospital, No.3, Jianshen Road, Tiedong District, Anshan, Liaoning Province PR China
                Article
                1966
                10.1186/s12885-015-1966-6
                4774000
                26931354
                944f3f2e-5d96-4006-9d12-0c323a0e4226
                © Cai et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 May 2015
                : 30 November 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                breast cancer,sln,non-sln,octamer binding factor,mskcc nomogram
                Oncology & Radiotherapy
                breast cancer, sln, non-sln, octamer binding factor, mskcc nomogram

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