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PubMed1995

Detection of proliferating cell nuclear antigen (PCNA) in canine and feline mammary tumours.

Quantitation of immunohistochemical staining of the proliferating cell nuclear antigen (PCNA, clone PC10) by image analysis was performed on benign and malignant mammary tumours of dogs and cats. Scoring of the slides was carried out by image analysis to assess the percentage of labelled nuclei (expressed as a ratio of areas). Either the strongly labelled nuclei (SP-PCNA index), or all of the stained nuclei (TP-PCNA index) were counted as positive to determine the growth fraction and its correlation with the histopathological classification and nuclear grade (degree of nuclear differentiation, considered a morphological correlate of tumour aggressiveness). A significant difference in the values of PCNA indices was seen between benign and malignant growths (P < 0.0001, dog; P < 0.05, cat). Neither of the PCNA indices showed correlation with nuclear grade in dogs (P = 0.14 for SP-PCNA index and P = 0.31 for TP-PCNA index) or cats (P = 0.09 for SP-PCNA index and P = 0.07 for TP-PCNA index). A significant difference in the number of mitoses, expressed as mitotic index, was seen between benign and malignant growths in the dog (P < 0.01) but not in the cat (P = 0.078). Good correlation of mitotic index with nuclear grade was revealed in canine malignant growths (P < 0.05), but in feline malignant tumours such correlation (P < 0.05) was shown only when the values of intermediate plus typical forms were compared with the data for atypical forms. It is concluded that quantitation of PCNA-positive nuclear area by image analysis provides an objective method for assessing proliferative activity in benign and malignant mammary tumours of dogs and cats.

Adenocarcinoma↗

PubMed1997

Immunohistochemical nuclear staining for p53, PCNA, and Ki-67 in different histologic variants of basal cell carcinoma.

BACKGROUND: Increased expression of p53 has been found in the majority of basal cell carcinomas (BCCs); however, UV-light-induced signature mutations are present in only about 50% of cases. Increased nuclear staining with an immunohistochemical marker of proliferation, proliferating cell nuclear antigen (PCNA), has been correlated with aggressive behavior in BCC. OBJECTIVE: Our purpose was to determine whether there is any relationship between different histologic variants of BCC and their expression of p53, PCNA, and Ki-67. METHODS: We used immunohistochemical stains for p53, PCNA, and Ki-67, in superficial-multicentric, nodular-noduloulcerative, sclerosing, infiltrative, and metatypical BCC, to determine whether the staining patterns differ in these different histologic variants of BCC. RESULTS: Superficial-multicentric BCCs were negative for p53 in four of eight tumors. Nodular BCC showed moderately intense p53 nuclear staining with some peripheral accentuation. PCNA nuclear staining was greater than Ki-67, and PCNA-positive cells were fewer than 10% in nodular BCC. Sclerosing and infiltrative BCC showed intense p53 nuclear staining with peripheral accentuation. PCNA nuclear staining was greater than Ki-67, and PCNA-positive cells were greater than 30% in the majority of these tumors. Metatypical BCCs showed diffuse intense p53 staining. PCNA nuclear staining was greater than Ki-67, and PCNA-positive cells were greater than 30% in all tumors studied. When overlying actinic keratoses showed p53 staining, the staining did not necessarily correlate with the intensity or even the presence of positive staining in the subjacent BCC. CONCLUSION: There are at least four distinctive patterns for staining of p53, PCNA, and Ki-67 that correlate with different histologic variants of BCC.

Biomarkers, Tumor↗

PubMed1998

Efficient PCNA complex formation is dependent upon both transcription coupled repair and genome overall repair.

The protein proliferating cell nuclear antigen (PCNA) is an auxiliary factor for DNA polymerase delta and is involved in the resynthesis step of nucleotide excision repair (NER). After UV irradiation of quiescent cells, PCNA forms an insoluble complex with nuclear substructures. We have investigated associations between NER and its subcomponent pathway, transcription coupled repair (TCR) on PCNA complex formation using genetically related hamster cell lines with different repair characteristics. In DNA repair proficient cells, the PCNA complex was readily detectable within 30 min after UV irradiation by both immunofluorescence and western blot analyses. This complex formation after UV occurs efficiently in quiescent cells. In UV5 (human XP-D homolog) and UV 24 (human XP-B homolog) cells, which are totally deficient in NER, the PCNA complex was not detectable at 30 min after UV. The PCNA complex formation is restored to normal levels in UV5 cells after transfection with the human XPD gene, encoding a subunit of the basal transcription factor, TFIIH. In UV61 (Human CS-B homolog) cells, that are defective only in transcription coupled repair (TCR) of cyclobutane pyrimidine dimers (CPDs), the rate of PCNA complex formation was 2-fold slower than in repair proficient cells. This defect was complemented by transfection of the CSB gene into the UV61 cells. We thus conclude that efficient PCNA complex formation after UV is dependent upon both the NER and TCR pathways in hamster cells. The association of several other DNA repair proteins including XPA, RPA, TFIIH and p53 with the insoluble PCNA complex in UV treated cells suggests a central role for PCNA in different steps of NER.

Animals↗

PubMed1994

Cip1 inhibits DNA replication but not PCNA-dependent nucleotide excision-repair.

BACKGROUND: DNA that is damaged by ultraviolet (UV) light is repaired predominantly by nucleotide excision-repair, a process requiring the DNA polymerase auxiliary factor PCNA. UV-irradiation also induces the production of Cip1 protein via activation of p53. Cip1 is an inhibitor of the cyclin-dependent kinases, which are required for the cell cycle to proceed through the G1/S-phase transition and initiate DNA replication. Inhibition by Cip1 probably causes the block to initiation of DNA replication that is seen in irradiated cells. Cip1 also directly inhibits the function of PCNA during DNA synthesis. As nucleotide excision-repair requires PCNA, the physiological relevance of PCNA inhibition by Cip1 is currently unclear. RESULTS: We show that nucleotide excision-repair of UV-damaged DNA occurs in extracts of Xenopus eggs, and that this reaction is PCNA-dependent. The repair reaction is not inhibited by Cip1, even when the level of PCNA is reduced 100-fold so that it becomes limiting for DNA repair. By contrast, Cip1 strongly suppresses the function of PCNA in replicative DNA synthesis under these conditions. CONCLUSIONS: Cip1 can potentially inhibit DNA replication in Xenopus egg extracts by inhibiting the cyclin-dependent kinase function required for the initiation of replication forks, and also by inhibiting PCNA function. The inhibition of PCNA is selective for its function in DNA replication, however, as Cip1 does not affect PCNA function in nucleotide excision-repair. The induction of Cip1 in response to DNA damage, therefore, allows repair to continue in the genome under conditions in which replication is severely inhibited.

Animals↗

PubMed2006

P21Cip1/WAF1 downregulation is required for efficient PCNA ubiquitination after UV irradiation.

p21(Cip1/WAF1) is a known inhibitor of the short-gap filling activity of proliferating cell nuclear antigen (PCNA) during DNA repair. In agreement, p21 degradation after UV irradiation promotes PCNA-dependent repair. Recent reports have identified ubiquitination of PCNA as a relevant feature for PCNA-dependent DNA repair. Here, we show that PCNA ubiquitination in human cells is notably augmented after UV irradiation and other genotoxic treatments such as hydroxyurea, aphidicolin and methylmethane sulfonate. Intriguingly, those DNA damaging agents also promoted downregulation of p21. While ubiquitination of PCNA was not affected by deficient nucleotide excision repair (NER) and was observed in both proliferating and arrested cells, stable p21 expression caused a significant reduction in UV-induced ubiquitinated PCNA. Surprisingly, the negative regulation of PCNA ubiquitination by p21 does not depend on the direct interaction with PCNA but requires the cyclin dependent kinase binding domain of p21. Taken together, our data suggest that p21 downregulation plays a role in efficient PCNA ubiquitination after UV irradiation.

Antineoplastic Agents↗

PubMed2004

Expression of p120, Ki-67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value.

The cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. The expression of these proteins by immunostaining methods was reported to be of value in determining the prognosis of patients with malignant diseases. In this study, we evaluated the prognostic significance of the expression of nuclear antigens p120, PCNA and Ki-67 in prostate cancer and compared the results with other prognostic factors. Imprint smear samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against p120, Ki-67 and PCNA. The immunostaining results were correlated with Gleason score, tumour differentiation, stage and prostatic specific antigen (PSA) levels. Our findings demonstrate that p120, Ki-67 and PCNA expression in prostatic carcinoma smears, correlated significantly with the degree of Gleason score (P < 0.001). When combining p120, Ki-67 and PCNA positivity with tumour differentiation there was a significant association among these parameters (P < 0.001). Overexpression of p120, Ki-67 and PCNA, was also associated with increased PSA serum levels (>4 ng/ml) (P < 0.001). The distribution of p120, Ki-67 and PCNA expression in prostate carcinomas was not statistically significant for Ki-67 (P = 0.69) and p120 (P = 0.22) but was significant for PCNA (P < 0.001) as far as the histological stage (T2a, T2b, T2c, T3a). P120, Ki-67 and PCNA expression had significant prognostic value for disease-free survival. Our results conclude that nuclear antigens p120, Ki-67 and PCNA appear to be additional markers in the field of prognosis of prostatic carcinoma.

Adult↗

PubMed1995

Comparison of proliferating cell nuclear antigen (PCNA) staining and BrdUrd-labelling index under different proliferative conditions in vitro by flow cytometry.

PC10 is a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The staining pattern in immunochemistry depends on fixation and detergent extraction treatment. The aim of this study was to validate the flow cytometric PCNA assay against Bromodeoxyuridine-labelling index (BrdUrd-LI) under different proliferative conditions in vitro. Expression of PCNA in methanol fixed cells with, and without, prior detergent extraction with EDTA/Triton was compared to BrdUrd-labelling index in NIH-3T3 fibroblasts and human Caski tumour cells in exponential phase and under confluent conditions. Serum stimulation and serum starvation conditions were studied. The results for BrdUrd-LI and PCNA-index after extraction showed good correlation for 3T3 fibroblasts and for Caski cells, with some differences for serum withdrawn Caski cells. There was no correlation between the number of cells that were positive for PCNA without extraction and BrdUrd-LI. Spheroid cells with G1-DNA-content showed an almost synchronous recruitment and progression through the cell cycle after trypsination and replating. Tightly bound PCNA paralleled this synchronicity whereas total PCNA did not change significantly. The results demonstrate that immunochemical detection of non-extractable PCNA-index gives similar results as compared with BrdUrd-labelling index under different proliferative conditions in vitro for different monolayer cell lines, whereas without extraction PCNA does not correlate with BrdUrd-LI in these fast growing cell lines due to its long half-life. PCNA expression parallels the progression through the cell cycle in V79 spheroids, a primitive model of tumour growth.

Animals↗

PubMed1997

PCNA and p53 in urinary bladder cancer: correlation with histological findings and prognosis.

BACKGROUND: This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. MATERIALS AND METHODS: The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and DO7 as the primary antibodies. Positive stainings were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with "low" and "high" scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into "low" and "high" score groups, and survival rates of the groups were compared. RESULTS: PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r = 0.67). CONCLUSIONS: PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.

Adult↗

PubMed1993

Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.

Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p << 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 +/- 28.4 [mean +/- standard deviation], PMM: 48.1 +/- 41.0, MMM: 117.0 +/- 64.6; Ki-67: BMN: 6.4 +/- 3.3, PMM 25.0 +/- 31.1, MMM: 95.2 +/- 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p << 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA-Breslow index: r = 0.42, p < 0.01; Ki-67-Breslow index: r = 0.60, p << 0.001; PCNA-mitotic rate: r = 0.40, p < 0.01; Ki-67-mitotic rate: r = 0.50, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1993

Prognostic significance of PCNA grade in malignant melanoma.

Proliferating cell nuclear antigen (PCNA) grade (a semi-quantitative assessment of the entire tumor profile) and estimation whether PCNA grade is low (0-50% positive cells) or high (51-100% positive cells) has been demonstrated to be of prognostic significance in gastric carcinoma. Sixteen vertical growth phase melanomas with 8 or more years of clinical follow-up were reacted with antibody to PCNA. PCNA grade was independently evaluated by both authors without knowledge of clinical outcome. PCNA grade was subsequently correlated with clinical outcome and other prognostic indicators. Agreement in assigning PCNA grade was noted between the two observers in 13/16 cases. However, PCNA grade failed to accurately predict patient survival or death. Additionally, PCNA grade was not significantly correlated with other recognized prognostic attributes. While interpretation of the prognostic significance of PCNA grade based upon this small series of cases should be conservative, a semi-quantitative estimate of PCNA-positive cells appears to have little utility in predicting the clinical outcome in malignant melanoma.

Antigens, Neoplasm↗

PubMed2005

A single domain in human DNA polymerase iota mediates interaction with PCNA: implications for translesion DNA synthesis.

DNA polymerases (Pols) of the Y family rescue stalled replication forks by promoting replication through DNA lesions. Humans have four Y family Pols, eta, iota, kappa, and Rev1, of which Pols eta, iota, and kappa have been shown to physically interact with proliferating cell nuclear antigen (PCNA) and be functionally stimulated by it. However, in sharp contrast to the large increase in processivity that PCNA binding imparts to the replicative Pol, Poldelta, the processivity of Y family Pols is not enhanced upon PCNA binding. Instead, PCNA binding improves the efficiency of nucleotide incorporation via a reduction in the apparent K(m) for the nucleotide. Here we show that Poliota interacts with PCNA via only one of its conserved PCNA binding motifs, regardless of whether PCNA is bound to DNA or not. The mode of PCNA binding by Poliota is quite unlike that in Poldelta, where multisite interactions with PCNA provide for a very tight binding of the replicating Pol with PCNA. We discuss the implications of these observations for the accuracy of DNA synthesis during translesion synthesis and for the process of Pol exchange at the lesion site.

Amino Acid Motifs↗

PubMed2001

UV-induced binding of ING1 to PCNA regulates the induction of apoptosis.

Previous studies have shown that UV-induced binding of p21(WAF1) to PCNA through the PCNA-interacting protein (PIP) domain in p21(WAF1) promotes a switch from DNA replication to DNA repair by altering the PCNA protein complex. Here we show that the p33(ING1b) isoform of the ING1 candidate tumour suppressor contains a PIP domain. UV rapidly induces p33(ING1b) to bind PCNA competitively through this domain, a motif also found in DNA ligase, the DNA repair-associated FEN1 and XPG exo/endonucleases, and DNA methyltransferase. Interaction of p33(ING1b) with PCNA occurs between a significant proportion of ING1 and PCNA, increases more than tenfold in response to UV and is specifically inhibited by overexpression of p21(WAF1), but not by p16(MTS1), which has no PIP sequence. In contrast to wild-type p33(ING1b), ING1 PIP mutants that do not bind PCNA do not induce apoptosis, but protect cells from UV-induced apoptosis, suggesting a role for this PCNA-p33(ING1b) interaction in eliminating UV-damaged cells through programmed cell death. These data indicate that ING1 competitively binds PCNA through a site used by growth regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of the PCNA protein complex.

Apoptosis↗

PubMed2002

[PCNA and Ki-67 expression in locally confined renal adenocarcinoma. Relationship with various histopathologic variables and prognostic significance].

OBJECTIVE: PCNA and Ki-67 expression are used as markers of cellular proliferation and different studies have investigated their value as prognostic indicators for renal adenocarcinoma. The aim of this study was to determine PCNA and Ki-67 expression in locally confined renal adenocarcinoma, their relationship with other histopathological variables and prognostic significance. METHODS: 58 cases of renal adenocarcinoma stages pT1-T3a N0 M0 (TNM 1997), treated by curative radical or partial nephrectomy were reviewed. The clinical and histopathological variables were analyzed. PCNA and Ki-67 expression in tissue embedded in paraffin were studied by immunohistochemical techniques. RESULTS: The mean percentage of nuclei that stained for PCNA was 7.03% (range 0-50%). Analysis of the correlation between PCNA and histopathological variables (size, grade and stage), showed a statistically significant correlation of PCNA only for the nuclear grade (p = 0.009). The mean percentage of nuclei that stained for Ki-67 expression was 2.96% (range 0-30%) and a relationship was found for size (p < 0.001), nuclear grade (p < 0.001) and stage (p < 0.001). The incidental clinical presentation, tumor size, stage, nuclear grade, PCNA and Ki-67 expression showed a relationship with survival. However, only perirenal fat infiltration, tumor size, nuclear grade and PCNA expression were found to be independent factors by multivariate analysis. CONCLUSIONS: PCNA expression correlated with nuclear grade, while Ki-67 demonstrated a significant correlation with tumor size, grade and stage. Survival analysis showed a relationship of both markers with prognosis. However, only PCNA was found to be an independent factor by multivariate analysis.

Adenocarcinoma↗

PubMed2004

[Expression of RFC2 and PCNA in different gestational trophoblastic diseases].

BACKGROUND & OBJECTIVE: High expression of replication factor C (RFC) mRNA in hydatidiform mole and choriocarcinoma were detected previously with DNA microarray. Replication factor C subunit 2 (RFC2) was reported to be associated with DNA duplication, DNA repair, and the function of cellular checkpoint. The aim of current study was to investigate the expression levels of RFC2 and proliferating cell nuclear antigen (PCNA) in gestational trophoblastic diseases (GTD) and to explore the relationship of expressions of two proteins with GTD. METHODS: The expression of RFC2 and PCNA were detected with immunohistochemical method in 15 cases of normal villi, 38 cases of hydatidiform moles (HM), 42 cases of invasive moles (IM), and 18 cases of choriocarcinomas (CC). RESULTS: The expression of RFC2 and PCNA were significantly increased in HM, IM, and CC than in normal villi (P=0.000 for RFC2,P=0.004 for PCNA). There was no significant difference of the expression of RFC2 among HM, IM, and CC. The PCNA expression was significantly higher in CC than in HM (P=0.037). PCNA expression was significantly higher in the patients with malignantly transformed molar pregnancy than in the patients without malignantly transformed molar pregnancy (P=0.039). RFC2 expression in no preoperative chemotherapeutic group of gestational trophoblastic tumors (GTT) including IM and CC was significantly higher than that in the group with the chemotherapy of more than 3 cycles (P=0.028). Compared with patients at stageI, patients at stage III (WHO) had significantly increased expression of RFC2 (P=0.01). The level of RFC2 was higher in the patients with high risk in WHO prognostic scoring system than that in the patients with low risk (P=0.018). The levels of PCNA were significantly higher in the patients with high risk and middle risk than that in the patients with low risk (P=0.036 and P=0.048, respectively). The expression of PCNA protein was not associated with the preoperative chemotherapy and WHO stage of GTT. The RFC2 expression was positively correlated with the PCNA expression (P=0.000). CONCLUSION: The over-expression of RFC2 and PCNA in GTD may be associated with the malignant transformation of HM and the behavior of trophoblastic tumor.

Adult↗

PubMed2005

[Expression and prognosis significance of p73 and PCNA in laryngeal squamous cell carcinoma].

OBJECTIVE: This study was designed to investigate the expression of p73 and Proliferating Cell Nuclear Antigen (PCNA) and their association with clinical, histologic characteristics and prognosis in LSCC. METHOD: p73 protein and PCNA protein were examined by using immunochistochemical SABC staining method in 65 cases of LSCC and in 23 adjacency carcinoma cases. RESULT: p73 protein and PCNA protein in LSCC shows stronger expression than that in adjacency carcinoma, which is statistically significant (P <0.05). p73 protein positive expression shows stronger in stage III approximately IVof LSCC than that in stage I approximately II (P<0.05); it more often appears in recurrent cases than in primary cases (P <0.05). And p73 protein positive expression with distant metastasis was stronger than that in LSCC without distant metastasis (P <0.05). PCNA protein positive expression was stronger in stage III approximately IV of LSCC than that in stage I approximately II (P <0.05); it more often appears in recurrent cases than in primary cases (P <0.05). PCNA protein positive expression more frequently appears in poor differentiation of LSCC, compared to well/mediate differentiation (P <0.05); PCNA positive expression in cases with cervical lymph node metastasis and distant metastasis was stronger than that without metastasis (P <0.05). PCNA expression had a significantly stronger in patients whose survival time over 5 years than that in patients whose survival time less than 5 years (P <0.05). Analysing with multivariate Cox, the expression of PCNA is an important marker of poor prognosis (RR= 2.43, P <0.05). CONCLUSION: p73 protein positive expression may play a part in LSCC progression and function as an oncogene in the development of LSCC. PCNA positive expression was closely linked with the risk of LSCC; it can be an important predictor on evaluating the prognosis of LSCC. There was positive correlation existing between p73 protein and PCNA protein expression in LSCC.

Adult↗

PubMed1993

[The evaluation of cellular proliferating activity in gastric carcinoma with the proliferating cell nuclear antigen (PCNA) expressive rate: its fundamental examination of the immunohistochemical procedures and its clinical applications].

PCNA is known as a cell cycle-related nuclear antigen. We stained PCNA immunohistochemically, and examined whether or not PCNA expressive rate could be applied clinically for a biological parameter of the histopathological effects in preoperative chemotherapy. PCNA was stained in proliferating cell by measuring nuclear DNA simultaneously. The most suitable fixation time in PCNA expression was 24 hours. On the examination of fixation fluid, ethanol was considered to be more suitable than buffer formaldehyde because PCNA expressive rate in ethanol correlated to BrdU labeling index with statistical significance. We examined PCNA expressive rate in gastric carcinomas. In the group whose histopathological effects of preoperative chemotherapy was recognized to be positive, PCNA expressive rate was significantly lower than in the group of negative effect. We measured thymidylate synthetase inhibition rate (TSIR) in the cases of preoperative oral administration of 5-FU, and the significantly negative correlation was seen between TSIR and PCNA expressive rate in the cases of differentiated adenocarcinoma (p < 0.05). The proliferating activity was recognized to be lower in the cases of higher inhibitional effect for DNA synthesis. PCNA expressive rate was considered to be a more effective and objective biological parameter on the evaluation of malignant potential in gastric carcinoma.

Antigens, Neoplasm↗

PubMed1998

Expression of proliferating cell nuclear antigen(PCNA) in biopsy and autopsy specimens of gastric carcinoma.

UNLABELLED: Although proliferating cell nuclear antigen (PCNA) is known to be an indicator of malignant potential in tumors, the biological and clinicopathological significance of PCNA in tumor tissue is controversial. METHODS: Immunohistochemical expression of PCNA was examined in 58 gastric carcinoma tissues obtained at autopsy to test the clinicopathological significance. In addition, in 24 of the 58 tumor tissues we compared immunohistochemical expression of PCNA in biopsy and autopsy specimens from the same patient in order to know whether the proliferating activity of tumor cells is stationary from the early stage to the end of tumor growth. RESULTS: 1. PCNA was undetectable in some tumor tissues (12.5% in biopsy and 10.3% in autopsy specimens). 2. the frequency of PCNA positive cases and labeling index (LI) (%) of PCNA in tumor tissues were not significantly different between biopsy and autopsy specimens. 3. the intensity of PCNA reaction was not related to prognosis. 4. PCNA positive cases and LI did not correlate with survival condition. CONCLUSION: It is hard to say whether PCNA is a reliable indicator in predicting malignancy and prognosis of gastric cancer.

Adult↗

PubMed2000

Single nucleotide polymorphism analyses of the human proliferating cell nuclear antigen (pCNA) and flap endonuclease (FEN1) genes.

The products of proliferating cell nuclear antigen (PCNA) and flap endonuclease (FEN1) genes are multifunctional proteins that are involved in DNA replication and damage repair. Yeast models suggest association of mutant forms of PCNA and FEN1 with genomic instability. In our study, we have determined the single nucleotide polymorphisms in human PCNA and FEN1 genes. We sequenced the coding region and adjacent noncoding region of both the PCNA and FEN1 genes in 120 alleles (60 individuals). In the PCNA gene, we detected 9 sequence variants with Hardy-Weinberg allele frequency ranging from 0.008 to 0.088. No polymorphism was detected in the FEN1 gene. The sequence variants in the PCNA gene included 7 intronic single nucleotide polymorphisms (SNP) and 2 synonymous exonic SNPs. All the intronic SNPs were located in introns 1 and 4, which contain several regulatory elements involved in the control of PCNA gene expression. Six of the 7 intronic SNPs showed complete linkage disequilibrium. We confirmed this allelic linkage disequilibrium by allele-specific PCR sequencing. We genotyped 117 additional individuals belonging to 3 population subgroups using the PCR-RFLP method. Finally, to see if the detected polymorphisms are associated with any cancer type, we genotyped cases with melanomas (37 cases), breast cancers (118 cases) and lung cancers (100 cases). We did not find statistical difference in frequency of polymorphism in any cancer type compared with healthy controls, although in breast cancer the frequency was low. Our results suggest that the coding regions of the PCNA and FEN1 genes are highly conserved when compared with other DNA repair genes. The potential of some of the detected intronic polymorphisms to effect regulation of the PCNA gene expression remains to be determined.

Alleles↗