Synaptonemal Complex

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Christer Hoog - One of the best experts on this subject based on the ideXlab platform.

  • The central element of the Synaptonemal Complex in mice is organized as a bilayered junction structure
    Journal of cell science, 2016
    Co-Authors: Abrahan Hernández-hernández, Anna Kouznetsova, Bertil Daneholt, Sergej Masich, Tomoyuki Fukuda, Sara Sandin, Christer Hoog
    Abstract:

    The Synaptonemal Complex transiently stabilizes pairing interactions between homologous chromosomes during meiosis. Assembly of the Synaptonemal Complex is mediated through integration of opposing transverse filaments into a central element, a process that is poorly understood. We have, here, analyzed the localization of the transverse filament protein SYCP1 and the central element proteins SYCE1, SYCE2 and SYCE3 within the central region of the Synaptonemal Complex in mouse spermatocytes using immunoelectron microscopy. Distribution of immuno-gold particles in a lateral view of the Synaptonemal Complex, supported by protein interaction data, suggest that the N-terminal region of SYCP1 and SYCE3 form a joint bilayered central structure, and that SYCE1 and SYCE2 localize in between the two layers. We find that disruption of SYCE2 and TEX12 (a fourth central element protein) localization to the central element abolishes central alignment of the N-terminal region of SYCP1. Thus, our results show that all four central element proteins, in an interdependent manner, contribute to stabilization of opposing N-terminal regions of SYCP1, forming a bilayered transverse-filament-central-element junction structure that promotes Synaptonemal Complex formation and synapsis.

  • Synaptonemal Complex Components Persist at Centromeres and Are Required for Homologous Centromere Pairing in Mouse Spermatocytes
    PLOS Genetics, 2012
    Co-Authors: C. Gastón Bisig, Michel F. Guiraldelli, Anna Kouznetsova, Harry Scherthan, Dean S. Dawson, Christer Hoog, Roberto J. Pezza
    Abstract:

    Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the Synaptonemal Complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the Synaptonemal Complex are retained at paired centromeres after disassembly of the Synaptonemal Complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as Synaptonemal Complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and, by doing so, improve the segregation fidelity of mammalian meiotic chromosomes.

  • meiosis in mice without a Synaptonemal Complex
    PLOS ONE, 2011
    Co-Authors: Anna Kouznetsova, Ricardo Benavente, Albert Pastink, Christer Hoog
    Abstract:

    The Synaptonemal Complex (SC) promotes fusion of the homologous chromosomes (synapsis) and crossover recombination events during meiosis. The SC displays an extensive structural conservation between species; however, a few organisms lack SC and execute meiotic process in a SC-independent manner. To clarify the SC function in mammals, we have generated a mutant mouse strain (Sycp1−/−Sycp3−/−, here called SC-null) in which all known SC proteins have been displaced from meiotic chromosomes. While transmission electron microscopy failed to identify any remnants of the SC in SC-null spermatocytes, neither formation of the cohesion axes nor attachment of the chromosomes to the nuclear membrane was perturbed. Furthermore, the meiotic chromosomes in SC-null meiocytes achieved pre-synaptic pairing, underwent early homologous recombination events and sustained a residual crossover formation. In contrast, in SC-null meiocytes synapsis and MLH1-MLH3-dependent crossovers maturation were abolished, whereas the structural integrity of chromosomes was drastically impaired. The variable consequences that SC inactivation has on the meiotic process in different organisms, together with the absence of SC in some unrelated species, imply that the SC could have originated independently in different taxonomic groups.

  • Progression of meiotic recombination requires structural maturation of the central element of the Synaptonemal Complex
    Journal of Cell Science, 2008
    Co-Authors: Geert Hamer, Howard J. Cooke, Ricardo Benavente, Hong Wang, Ewelina Bolcun-filas, Christer Hoog
    Abstract:

    The Synaptonemal Complex is an elaborate meiosis-specific supramolecular protein assembly that promotes chromosome synapsis and meiotic recombination. We inactivated the meiosis-specific gene Tex12 and found that TEX12 is essential for progression of meiosis in both male and female germ cells. Structural analysis of the Synaptonemal Complex in Tex12-/- meiocytes revealed a disrupted central element structure, a dense structure residing between the synapsed homologous chromosomes. Chromosome synapsis is initiated at multiple positions along the paired homologous chromosomes in Tex12-/- meiotic cells, but fails to propagate along the chromosomes. Furthermore, although meiotic recombination is initiated in Tex12-/- meiotic cells, these early recombination events do not develop into meiotic crossovers. Hence, the mere initiation of synapsis is not sufficient to support meiotic crossing-over. Our results show that TEX12 is a component of the central element structure of the Synaptonemal Complex required for propagation of synapsis along the paired homologous chromosomes and maturation of early recombination events into crossovers.

  • characterization of a novel meiosis specific protein within the central element of the Synaptonemal Complex
    Journal of Cell Science, 2006
    Co-Authors: Geert Hamer, Anna Kouznetsova, Ricardo Benavente, Ivana Novak, Katarina Gell, Christer Hoog
    Abstract:

    During the first meiotic prophase, alignment and synapsis of the homologous chromosomes are mediated by the Synaptonemal Complex. Incorrect assembly of this Complex results in cell death, impaired meiotic recombination and formation of aneuploid germ cells. We have identified a novel mouse meiosis-specific protein, TEX12, and shown it to be a component of the central element structure of the Synaptonemal Complex at synapsed homologous chromosomes. Only two other central element proteins, SYCE1 and SYCE2, have been identified to date and, using several mouse knockout models, we show that these proteins and TEX12 specifically depend on the Synaptonemal transverse filament protein SYCP1 for localization to the meiotic chromosomes. Additionally, we show that TEX12 exactly co-localized with SYCE2, having the same, often punctate, localization pattern. SYCE1, on the other hand, co-localized with SYCP1 and these proteins displayed the same more continuous expression pattern. These co-localization studies were confirmed by co-immunoprecipitation experiments that showed that TEX12 specifically co-precipitated with SYCE2. Our results suggest a molecular network within the central elements, in which TEX12 and SYCE2 form a Complex that interacts with SYCE1. SYCE1 interacts more directly with SYCP1 and could thus anchor the central element proteins to the transverse filaments.

Haruhisa Kitano - One of the best experts on this subject based on the ideXlab platform.

  • abstract 5184 Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non small cell lung cancer
    Cancer Research, 2015
    Co-Authors: Haruhisa Kitano, Joon-yong Chung, Jun Hanaoka, Junya Fukuoka, Shuhei Inoue, Doki Yoshinori, Stephen M. Hewitt
    Abstract:

    Lymphangiogenesis is a key component for tumor growth and metastasis in non-small cell lung cancer (NSCLC), and is a promising target in cancer therapy strategy. The axis of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGFR-3 is considered to be a major driver of lymphangiogenesis but the detailed mechanism of this process remains unclear. We recently showed that the expression of Synaptonemal Complex protein 3 (SCP3) is associated with poor prognosis and linked with lymph node metastasis in NSCLC. To investigate the possible lymphangiogenic significance of SCP3 in NSCLC, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expressions in archival tumor tissues from 89 NSCLC patients with lymph node metastasis by immunohistochemical staining. The positive staining of SCP3, VEGF-A, VEGF-B, VEGF-C and VEGF-D expressions were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, we have identified that the SCP3 expression is positively correlated with VEGF-C and VEGF-D (for both, p Citation Format: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt. Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2015-5184

  • Synaptonemal Complex protein 3 as a novel prognostic marker in early stage non small cell lung cancer
    Human Pathology, 2013
    Co-Authors: Joon-yong Chung, Haruhisa Kitano, Mikiko Takikita, Hanbyoul Cho, Kyung Hee Noh, Tae Woo Kim, Kris Ylaya
    Abstract:

    Synaptonemal Complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of Synaptonemal Complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between Synaptonemal Complex protein 3 and various clinicopathologic parameters, we assessed the expression of Synaptonemal Complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, Synaptonemal Complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, Synaptonemal Complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal Complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased Synaptonemal Complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive Synaptonemal Complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.

  • Synaptonemal Complex protein 3 as a novel prognostic marker in early stage non–small cell lung cancer
    Human pathology, 2012
    Co-Authors: Joon-yong Chung, Haruhisa Kitano, Mikiko Takikita, Hanbyoul Cho, Kyung Hee Noh, Tae Woo Kim, Kris Ylaya, Jun Hanaoka, Junya Fukuoka, Stephen M. Hewitt
    Abstract:

    Synaptonemal Complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of Synaptonemal Complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between Synaptonemal Complex protein 3 and various clinicopathologic parameters, we assessed the expression of Synaptonemal Complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, Synaptonemal Complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, Synaptonemal Complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal Complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased Synaptonemal Complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive Synaptonemal Complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.

Shirleen G Roeder - One of the best experts on this subject based on the ideXlab platform.

  • the Synaptonemal Complex protein zip1 promotes the segregation of nonexchange chromosomes at meiosis i
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Louise Newnham, Philip W Jordan, Beth Rockmill, Shirleen G Roeder, Eva R Hoffmann
    Abstract:

    Crossing over establishes connections between homologous chromosomes that promote their proper segregation at the first meiotic division. However, there exists a backup system to ensure the correct segregation of those chromosome pairs that fail to cross over. We have found that, in budding yeast, a mutation eliminating the Synaptonemal Complex protein, Zip1, increases the meiosis I nondisjunction rate of nonexchange chromosomes (NECs). The centromeres of NECs become tethered during meiotic prophase, and this tethering is disrupted by the zip1 mutation. Furthermore, the Zip1 protein often colocalizes to the centromeres of the tethered chromosomes, suggesting that Zip1 plays a direct role in holding NECs together. Zip3, a protein involved in the initiation of Synaptonemal Complex formation, is also important for NEC segregation. In the absence of Zip3, both the tethering of NECs and the localization of Zip1 to centromeres are impaired. A mutation in the MAD3 gene, which encodes a component of the spindle checkpoint, also increases the nondisjunction of NECs. Together, the zip1 and mad3 mutations have an additive effect, suggesting that these proteins act in parallel pathways to promote NEC segregation. We propose that Mad3 promotes the segregation of NECs that are not tethered by Zip1 at their centromeres.

  • zip3 provides a link between recombination enzymes and Synaptonemal Complex proteins
    Cell, 2000
    Co-Authors: Seema Agarwal, Shirleen G Roeder
    Abstract:

    In budding yeast, absence of the meiosis-specific Zip3 protein (also known as Cst9) causes Synaptonemal Complex formation to be delayed and incomplete. The Zip3 protein colocalizes with Zip2 at discrete foci on meiotic chromosomes, corresponding to the sites where synapsis initiates. Observations suggest that Zip3 promotes synapsis by recruiting the Zip2 protein to chromosomes and/or stabilizing the association of Zip2 with chromosomes. Zip3 interacts with a number of gene products involved in meiotic recombination, including proteins that act at both early (Mre11, Rad51, and Rad57) and late (Msh4 and Msh5) steps in the exchange process. We speculate that Zip3 is a component of recombination nodules and serves to link the initiation of synapsis to meiotic recombination.

  • crossover interference is abolished in the absence of a Synaptonemal Complex protein
    Cell, 1994
    Co-Authors: Mary Sym, Shirleen G Roeder
    Abstract:

    In the zip1 mutant, meiotic chromosomes fail to synapse, owing to the absence of a structural component of the Synaptonemal Complex (SC). This mutant has been analyzed for the ability to carry out several functions that have been proposed for the SC. The data presented show that the zip1 mutation does not affect chiasma function and confers only modest defects in meiotic recombination and sister chromatid cohesion. In contrast, crossover interference is completely abolished in the absence of Zip1. These data are the first to establish a molecular link between cytological observations of the SC and the genetic phenomenon of interference.

  • zip1 is a Synaptonemal Complex protein required for meiotic chromosome synapsis
    Cell, 1993
    Co-Authors: Mary Sym, Joanne Engebrecht, Shirleen G Roeder
    Abstract:

    Abstract ZIP1 is a novel meiosis-specific gene required for chromosome synapsis and cell cycle progression in S. cerevlsiae. zip1 strains undergo homologous chromosome pairing, but are defective in Synaptonemal Complex (SC) formation. The zip1 mutation confers a uniform arrest in meiosis prior to the first division. zip1 strains display nearly wild-type levels of commitment to melotic recombination; however, mature reciprocal recombinants are not formed until cells are released from meiotic arrest by return to growth medium. DNA sequence analysis of ZIP1 reveals structural homology to a number of proteins containing coiled coils. Immunofluorescence experiments using anti-ZIP1 antibodies demonstrate that the ZIP1 protein localizes to synapsed meiotic chromosomes but not to unsynapsed axial elements. Taken together, these data suggest that ZIP1 is a component of the central region of the SC. We propose a model in which ZIP1 acts as a molecular zipper to bring homologous chromosomes in close apposition.

Stephen M. Hewitt - One of the best experts on this subject based on the ideXlab platform.

  • abstract 5184 Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non small cell lung cancer
    Cancer Research, 2015
    Co-Authors: Haruhisa Kitano, Joon-yong Chung, Jun Hanaoka, Junya Fukuoka, Shuhei Inoue, Doki Yoshinori, Stephen M. Hewitt
    Abstract:

    Lymphangiogenesis is a key component for tumor growth and metastasis in non-small cell lung cancer (NSCLC), and is a promising target in cancer therapy strategy. The axis of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGFR-3 is considered to be a major driver of lymphangiogenesis but the detailed mechanism of this process remains unclear. We recently showed that the expression of Synaptonemal Complex protein 3 (SCP3) is associated with poor prognosis and linked with lymph node metastasis in NSCLC. To investigate the possible lymphangiogenic significance of SCP3 in NSCLC, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expressions in archival tumor tissues from 89 NSCLC patients with lymph node metastasis by immunohistochemical staining. The positive staining of SCP3, VEGF-A, VEGF-B, VEGF-C and VEGF-D expressions were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, we have identified that the SCP3 expression is positively correlated with VEGF-C and VEGF-D (for both, p Citation Format: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt. Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2015-5184

  • Synaptonemal Complex protein 3 as a novel prognostic marker in early stage non–small cell lung cancer
    Human pathology, 2012
    Co-Authors: Joon-yong Chung, Haruhisa Kitano, Mikiko Takikita, Hanbyoul Cho, Kyung Hee Noh, Tae Woo Kim, Kris Ylaya, Jun Hanaoka, Junya Fukuoka, Stephen M. Hewitt
    Abstract:

    Synaptonemal Complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of Synaptonemal Complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between Synaptonemal Complex protein 3 and various clinicopathologic parameters, we assessed the expression of Synaptonemal Complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, Synaptonemal Complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, Synaptonemal Complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal Complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased Synaptonemal Complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive Synaptonemal Complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.

Joon-yong Chung - One of the best experts on this subject based on the ideXlab platform.

  • abstract 5184 Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non small cell lung cancer
    Cancer Research, 2015
    Co-Authors: Haruhisa Kitano, Joon-yong Chung, Jun Hanaoka, Junya Fukuoka, Shuhei Inoue, Doki Yoshinori, Stephen M. Hewitt
    Abstract:

    Lymphangiogenesis is a key component for tumor growth and metastasis in non-small cell lung cancer (NSCLC), and is a promising target in cancer therapy strategy. The axis of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGFR-3 is considered to be a major driver of lymphangiogenesis but the detailed mechanism of this process remains unclear. We recently showed that the expression of Synaptonemal Complex protein 3 (SCP3) is associated with poor prognosis and linked with lymph node metastasis in NSCLC. To investigate the possible lymphangiogenic significance of SCP3 in NSCLC, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expressions in archival tumor tissues from 89 NSCLC patients with lymph node metastasis by immunohistochemical staining. The positive staining of SCP3, VEGF-A, VEGF-B, VEGF-C and VEGF-D expressions were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, we have identified that the SCP3 expression is positively correlated with VEGF-C and VEGF-D (for both, p Citation Format: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt. Synaptonemal Complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2015-5184

  • Synaptonemal Complex protein 3 as a novel prognostic marker in early stage non small cell lung cancer
    Human Pathology, 2013
    Co-Authors: Joon-yong Chung, Haruhisa Kitano, Mikiko Takikita, Hanbyoul Cho, Kyung Hee Noh, Tae Woo Kim, Kris Ylaya
    Abstract:

    Synaptonemal Complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of Synaptonemal Complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between Synaptonemal Complex protein 3 and various clinicopathologic parameters, we assessed the expression of Synaptonemal Complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, Synaptonemal Complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, Synaptonemal Complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal Complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased Synaptonemal Complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive Synaptonemal Complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.

  • Synaptonemal Complex protein 3 as a novel prognostic marker in early stage non–small cell lung cancer
    Human pathology, 2012
    Co-Authors: Joon-yong Chung, Haruhisa Kitano, Mikiko Takikita, Hanbyoul Cho, Kyung Hee Noh, Tae Woo Kim, Kris Ylaya, Jun Hanaoka, Junya Fukuoka, Stephen M. Hewitt
    Abstract:

    Synaptonemal Complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of Synaptonemal Complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between Synaptonemal Complex protein 3 and various clinicopathologic parameters, we assessed the expression of Synaptonemal Complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, Synaptonemal Complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, Synaptonemal Complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal Complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased Synaptonemal Complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive Synaptonemal Complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.