Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis

Kawai, Toshiaki; Suzuki, Minoru; Kono, Suminori; Shinomiya, Nariyoshi; Rokutanda, Makoto; Takagi, Keigo; Ogata, Tetsuya; Tamai, Susumu

doi:10.1002/1097-0142(19941101)74:9<2468::aid-cncr2820740913>3.0.co;2-x

Cited by 56 publications

(28 citation statements)

References 25 publications

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“…Immunohistochemistry used to reveal Ki-67 protein was not always performed with the same antibody: clone Mib-1 in the majority of the studies (Costes et al, 1995;Bohm et al, 1996;Fontanini et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Minami et al, 2002;Rigau et al, 2002), antibodies coming from a firm selling several clones but without mention of the clone used (Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Giaccone et al, 1995;Pujol et al, 1996;Mehdi et al, 1998;Soomro et al, 1998;Carbognani et al, 2002); any mention of the antibodies used (Tungekar et al, 1991;Harpole Jr et al, 1995Giatromanolaki et al, 1996a, b;D'Amico et al, 1999D'Amico et al, , 2000Carvalho et al, 2000;Pelosi et al, 2001)…”

Section: Discussionmentioning

confidence: 99%

“…In total, 42 studies published between 1991 and 2002 were selected for this systematic review (Tungekar et al, 1991;Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Costes et al, 1995;Giaccone et al, 1995;Harpole, Jr et al, 1995Bohm et al, 1996;Fontanini et al, 1996;Giatromanolaki et al, 1996a, b;Pujol et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Mehdi et al, 1998;Soomro et al, 1998;D'Amico et al, 1999D'Amico et al, , 2000Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Carvalho et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Pelosi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Carbognani et al, 2002;Minami et al, 2002;Rigau et al, 2002). Five were excluded because an identical patients cohort was used in another selected publication (references excluded/includ...…”

Section: Studies Characteristicsmentioning

confidence: 99%

“…The reasons for not including these studies in the meta-analysis were the following: no survival curve shown (n ¼ 2) (Bellotti et al, 1997;Carvalho et al, 2000); no P-value, HR or CI reported (n ¼ 8) (Kawai et al, 1994;Giatromanolaki et al, 1996a;Bellotti et al, 1997;Komaki et al, 1998;Santinelli et al, 1999;Hayashi et al, 2001;Ramnath et al, 2001;Carbognani et al, 2002); distribution of Ki-67 status not reported (n ¼ 11) (Tungekar et al, 1991;Kawai et al, 1994;Giaccone et al, 1995;Bellotti et al, 1997;Komaki et al, 1998;Soomro et al, 1998;Dazzi et al, 1999;Dingemans et al, 2001;Ferreira et al, 2001;Pelosi et al, 2001;Rigau et al, 2002).…”

Section: Studies Characteristicsmentioning

confidence: 99%

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Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30 -1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

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Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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“…PCNA is a nuclear protein acting as a cofactor for DNA polymerase delta (Mathews et al, 1984). PCNA has been used as a proliferation and prognostic marker in a variety of malignancies, including lung tumors (Kawai et al, 1994) and it is an important prognostic factor of clinical outcome in patients with NSCLC (Volm and Koomagi, 2000).…”

Section: Discussionmentioning

confidence: 99%

pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis

Russo

Claudio

et al. 2003

Oncogene

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The retinoblastoma gene family consisting of RB/p105, p107, and RB2/p130 cooperate to regulate cell-cycle progression through the G1 phase of the cell cycle. Previous data demonstrated an independent role for the reduction or loss of pRb2/p130 expression in the formation and/or progression of lung carcinoma. Rb2/ p130 is mutated in a human cell line of lung small cell carcinoma as well as in primary lung tumors. To identify potential pRb2/p130 target genes in an unbiased manner, we have utilized an adenovirus-mediated expression system of pRb2/p130 in a non-small lung cancer cell line to identify specific genes that are regulated by pRb2/p130. Using oligonucleotide arrays, a number of Rb2/p130 downregulated genes were identified and their regulation was confirmed by semiquantitative reverse transcriptionpolymerase chain reaction (RT-PCR) and Western blot analysis. As a result, 40 genes showed greater than 2.0-fold modification in their expression level after the RB2/ p130 viral transduction. In conclusion, coupling adenoviral overexpression with microarray and semiquantitative RT-PCR analyses proved to be a versatile strategy for identifying pRb2/p130 target genes and for better understanding the expression profiles of these genes. Our results may also contribute to identifying novel therapeutic biomarkers in lung carcinoma.

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“…26 They investigated a relationship between PCNA and sex, age, tumor stage, survival, histologic type, degree of cell differantion and cellularity. They found that there was concordance between PCNA and clinical stage, cellularity and DNA content.…”

Section: Discussionmentioning

confidence: 99%

p53 Expression in Non–Small Cell and Small Cell Lung Carcinomas: Relationship with Proliferating Cell Nuclear Antigen and Cigarette Smoking

Karpuzoğlu

2001

Annals of Saudi Medicine

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The p53 gene is a tumor suppressor gene which is located on band 13p of chromosome 17. It encodes a 53-kd nuclear phosphoprotein, and has been found in all mammalian cells. It is thought to play a role in the control of the cell cycle. The wild type p53 protein inhibits cell proliferation by arresting cells in the G1 phase of the cell cycle, and loss of this activity can lead to neoplastic transformation.1-3 Mutations in p53 gene are the most common genetic alterations in several human malignancies, including lung, breast, colorectal, ovarian and cutaneous neoplasms, although the prognostic value of altered p53 expression is still debated. [4][5][6] Under physiological conditions, the wild type protein has a short half-life to allow immunohistochemical detection.7 However, the mutant type is more stable than the wild type, and is detectable in cell nuclei by standard immunohistochemical staining procedures. 1,7 To investigate the role of p53 in cell proliferation, we focused on markers of the cell cycle whose expression could be correlated with p53 immunohistochemical detection. One such marker is the proliferating cell nuclear antigen (PCNA). PCNA is a 36-kd nuclear polypeptide that is related to cell proliferation. PCNA, an auxilliary protein for DNA polymerase, is identical to cyclin, synthesized during the late G1 to S phase. The synthesis of PCNA is reported to be directly correlated with DNA replication and cell proliferation. 8,9 Our hypothesis was that p53 overexpression may be associated with increased cell proliferation, which might affect the clinical outcome of non-small cell lung carcinomas (NSCLC) and small cell lung carcinomas (SCLC). We examined the expression of p53 and PCNA immunohistochemically. The aim of this study was to evaluate the relationship of p53 and age, sex, nodal involvement, tumor stage, tumor size and proliferative activity in NSCLC and SCLC. Materials and MethodsThis study was based on 60 cases of primary lung carcinoma taken from the files of the Pathology Department, School of Medicine, Akdeniz University. Tumor tissue was obtained by biopsy (n=22, SCLC) or surgical resection (n=30, NSCLC and n=8, SCLC). The pathologic features of the surgical specimens were classified and staged according to the World Health Organization criteria and TNM staging system. Cases of NSCLS consisting of 24 squamous, 1 adenosquamous and 5 adenocarcinomas were examined. In the resection specimens, the size of the tumor and the tumor stage, vessel and nerve invasion, lymph node and pleura involvement were evaluated.All specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Sections were cut into 5 μ pieces, mounted on glass and dried overnight at 37°C. All sections were then deparaffinized in xylene, rehydrated through alcohol and washed in phosphate-buffered saline. This buffer was used for all subsequent washes and for dilution of the antibodies. Sections for p53 detection were heated in a microwave oven twice for 5 minutes at 700 W in citrate buffer (pH: 6). Mono...

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Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis

Cited by 56 publications

References 25 publications

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis

p53 Expression in Non–Small Cell and Small Cell Lung Carcinomas: Relationship with Proliferating Cell Nuclear Antigen and Cigarette Smoking

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