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F Basolo

Publications and source records attributed to F Basolo.

At least 73 records · Page 4Linked to original sources
PubMed1996

Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma.

Oncogenic rearrangements of RET and NTRK1 proto-oncogenes are frequently detected in papillary thyroid carcinomas. Several studies have shown an association between ionizing radiation and development of this tumor type. In addition in vitro irradiation of tumor cell lines induced rearrangements of RET similar to those observed in human papillary thyroid carcinomas. These two observations could be related to the reported increased incidence of papillary thyroid carcinomas in children living in contaminated areas around Chernobyl, given that it has been demonstrated that about 60% of them presents a RET oncogenic activation. However, this high frequency of RET positivity in radiation exposed children does not rule out the possibility that age could also play a role in the development of RET positive tumors. To assess this possibility we looked for a relationship between the presence of RET and NTRK1 oncogenic rearrangements and age at surgery in a sample of 92 consecutive patients. Our results show that, in papillary thyroid carcinoma, the frequency of RET and NTRK1 activation is significantly higher in the group of patients aged 4-30 years, thas supporting the concept that age could be contributing to this thyroid specific carcinogenic process.

3T3 Cells↗
PubMed1996

Phenylacetate inhibits protein isoprenylation and growth of the androgen-independent LNCaP prostate cancer cells transfected with the T24 Ha-ras oncogene.

The refractoriness of prostate cancer to androgen suppression is the landmark of clinically aggressive disease. In this study, the androgen-dependent LNCaP prostate cancer cells were transfected with the mutated c-Ha-ras gene from the T24 human bladder cancer. The derivative clone overexpressing T24-ras (LNCaP(T24-ras)) proliferated in androgen-depleted medium and showed increased growth. Protein isoprenylation and p21ras farnesylation in LNCaP(T24-ras) cells were tested in the presence of phenylacetate to document a possible relationship with the drug-induced inhibition of cell proliferation. Phenylacetate is a differentiation inducer that down-regulates in vitro the expression of the myc oncogene and activates the human peroxisome proliferator-activated nuclear receptor involved in cell growth regulation. The drug inhibited protein isoprenylation and p21ras farnesylation in LNCaP(T24-ras) cells; IC50 values were 3.1 and 3.3 mM, respectively, compared with controls. The drug reduced the cellular levels of endogenous farnesyl-PP (mean IC50 = 3.5 mM) and inhibited activation of the p21ras downstream target, p42(MAPK)/ERK2. LNCaP(T24-ras) was more sensitive than the parental line to both growth inhibition (mean IC50 = 3.01 and 7.1 mM, respectively) and apoptosis by phenylacetate. Exogenous farnesyl- and geranylgeranyl-PP indeed reduced the effects of the drug on proliferation and apoptosis in LNCaP(T24-ras) cells. In conclusion, the inhibition of protein isoprenylation and p21ras farnesylation by phenylacetate resulted in increased chemosensitivity of the androgen-independent LNCaP(T24-ras) cells compared with LNCaP, and this effect might contribute to the pharmacological activity of the drug.

Antimetabolites, Antineoplastic↗
PubMed1996

Microvessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma.

The growth of newly formed vessels (neoangiogenesis) represents an important step both in physiologic and pathologic situations. In particular, tumor growth and metastasis require angiogenesis. Microvessel count, which expresses a measure of tumor angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head, neck, and pulmonary cancer. In this study, the role of tumor angiogenesis as a prognostic indicator was examined in 157 primary thyroid cancers including 82 well-differentiated carcinomas, 52 medullary carcinomas, and 23 undifferentiated carcinomas. Microvessels were carefully counted by highlighting endothelial cells with anti-CD34 formalin-fixed tumor samples. The mean of microvessel count was 30.7 per field in papillary thyroid carcinomas, 39.4 per field in follicular thyroid carcinomas, 32.7 per field in undifferentiated carcinoma, and 41.8 per field in medullary carcinoma. We found that the number of newly formed vessels was significantly associated with poor prognosis only in medullary carcinoma. All of the dead patients with medullary carcinoma showed a microvessel count higher than 30, which resulted in a high statistical difference compared with alive patients (P = 0.00098). Multiple logistic regression analysis showed microvessel count, together with pTNM (P = 0.026). These results were also confirmed by Kaplan-Meir survival analysis (log-rank test; P = 0.04). By contrast, no differences in the number of microvessels was found between dead and living patients with well-differentiated carcinoma and undifferentiated carcinoma. In conclusion, microvessel count, as quantitation of tumor angiogenesis, plays an important prognostic role in medullary thyroid carcinomas.

Adolescent↗
PubMed1996

Expression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study.

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers.

Adult↗
PubMed1995

Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes.

Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

Animals↗
PubMed1995

NM23 gene expression correlates with cell growth rate and S-phase.

Two human NM23 genes have been identified: NM23.H1 and NM23.H2 coding for the A and B subunit of a nucleoside diphosphate kinase (NDPK), respectively. NM23.H1 gene has been proposed as a suppressor of metastatic ability in tumor cells, NM23.H2 is identical to the c-myc transcription factor, PuF. The NM23 coding sequence is strongly preserved through different species. Indirect evidence of various types has been accumulated and seems to support an implication of NM23 in cell proliferation. This report shows that the NM23 gene expression is strictly related to the growth state of the cells. Two different in vitro systems (human peripheral blood lymphocytes and human breast epithelial cell line MCF-10A) and one in vivo (human primary infiltrating ductal breast carcinomas) system have been investigated. The mRNA is present in PHA-stimulated peripheral blood lymphocytes, whereas it is nearly undetectable in their resting counterparts. The level of the NM23 gene expression parallels the fraction of cells incorporating thymidine (S-phase) in neoplastic mammary tissues. In synchronously cycling MCF-10A cells NM23.H1 mRNA reaches a maximum abundance in the S-phase and is absent or only present at very low levels during G0/G1 phase, whereas NM23.H2 is present in growth-arrested cells but is upregulated following serum growth stimulation.

Breast↗
PubMed1995

Productive HIV-1 infection of human vascular endothelial cells requires cell proliferation and is stimulated by combined treatment with interleukin-1 beta plus tumor necrosis factor-alpha.

Vascular endothelial cells (EC) play a key role in viral tropism in vivo. Since conflicting reports have been published on the capability of HIV to infect EC in vitro, we analyzed some factors potentially capable of influencing the susceptibility of human umbilical vein endothelial cells (HUVEC) to HIV-1. Both primary cultures and differentiated immortalized HUVEC lines were used. HUVEC were negative for the expression of CD4, but weakly CD26- and galactosylceramide-positive. Although binding of HIV to EC was substantial, the virus was apparently incapable of replicating in nonproliferating cultures. In resting cultures, the content of cell-associated HIV disappeared 4-6 days after infection without production of p24 and infectious progency. In contrast, infection of proliferating EC cultures led to the transient release of p24 and infectious virus (10(2.5)-10(3.5) SFU/ml) peaking 2-6 days postinfection. Antibody neutralization of cytokines that may be produced by EC (IL1, IL6, IL8, TNF, IFN-beta) failed to modify virus adsorption and replication, whereas treatment with IL1-beta plus TNF-alpha stimulated both virus binding and virus release. As seen by gag polymerase chain reaction (PCR), the viral genome persisted up to 15 days in untreated EC cultures, but over 20 days in cultures exposed to IL1-beta plus TNF-alpha. This study shows that: (a) CD4-negative HUVEC are capable of binding substantial amounts of HIV-1; (b) binding is enhanced by proinflammatory cytokines; (c) the establishment of productive infection is favored by cell proliferation; and (d) exposure to IL1-beta plus TNF-alpha enhances virus replication.

CD4 Antigens↗
PubMed1995

Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype.

Epidermal growth factor receptor (EGFr) levels were evaluated in paraffin-embedded tumour specimens of non-small cell lung cancer (NSCLC) from 176 patients who underwent surgical resection. The EGFr expression was evaluated by immunocytochemical assay using a monoclonal antibody which recognises the external domain of the receptor. EGFr immunoreactivity was significantly higher in squamous than in non-squamous cell carcinomas (P = 0.0009). Hilar and/or mediastinal nodal involvement was found in 29 of 105 (27.4%) squamous cancers, and in this group of patients, the mean of EGFr positive cells was significantly higher than that of patients without nodal involvement (P = 0.01). No significant correlations were found between the expression of EGFr and other clinicopathological or biological parameters such as T-status, grading, proliferative activity. EGFR is suggested to represent a useful indicator of nodal metastasis in NSCLC.

Adenocarcinoma↗
PubMed1995

Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations.

BACKGROUND: Germline missense point mutations of the ret proto-oncogene have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC). Most of the mutations are found in exon 10, 11, or 16 of the gene and are easily recognized by restriction analysis. METHODS: Using restriction analysis, we screened 58 subjects from nine kindreds. RESULTS: Family members (n = 16) already known to be affected with the disease carried the germline mutation. Among the 42 subjects apparently unaffected, 37 were not gene carriers and 5 were gene carriers. Basal and pentagastrin-stimulated serum calcitonin levels were normal in two patients and abnormal in three. All patients were treated with total thyroidectomy and central node dissection. In all cases multiple foci of MTC were shown at histologic examination. CONCLUSIONS: Our data indicate that genetic screening of MEN2 pedigrees allows the early identification of gene carriers. Because surgery of MTC in the preclinical phase has high probability of curing these patients, we suggest genetic screening soon after birth and total thyroidectomy in gene carriers as early as possible.

Base Sequence↗
PubMed1995

Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.

Aged↗
PubMed1995

p53-dependent and p53-independent activation of apoptosis in mammary epithelial cells reveals a survival function of EGF and insulin.

The p53 tumor suppressor protein has been implicated as a mediator of programmed cell death (PCD). A series of nontransformed mammary epithelial cell (MEC) lines were used to correlate p53 function with activation of PCD. Treatment of MECs expressing mutant, inactive, or no p53 with DNA-damaging agents did not induce apoptosis. Upon introduction of temperature-sensitive p53 into HC11 cells, which lack wild-type (wt) p53, PCD was observed after mitomycin treatment at 32 degrees, when the ts p53 protein is in wt conformation. Thus, wt p53 mediates activation of PCD in response to mitomycin in HC11 cells. Treatment of the MCF10-A cells, which express wt p53, with various DNA-damaging agents led to nuclear accumulation of p53. Only mitomycin treatment led to an increase in the number of apoptotic nuclei. ErbB-2-transformed MCF10-A cells responded to mitomycin, cisplatin, and 5-Fl-uracil, suggesting that signaling from activated ErbB-2 enhances the cells ability to respond to DNA damage. A combination of high cell density and serum-free medium induces apoptosis in all MECs tested, irrespective of their p53 status. Under these conditions, EGF or insulin act as survival factors in preventing PCD. These data might elucidate some aspects of breast involution and tumorigenesis.

Animals↗
PubMed1995

Productive HIV-1 infection of normal human mammary epithelial cells.

OBJECTIVE AND DESIGN: To determine the susceptibility of mammary epithelial cells (MEC) to HIV-1 as breastfeeding is an established route of HIV transmission, although the origin of virus in breastmilk is unclear. METHODS: Primary epithelial cell cultures were derived from the mammary glands of healthy donors; immortalized MEC lines were also used. HIV infection was followed by detection of infectious particle production, p24 antigen and viral sequences. RESULTS: Seven out of 11 primary MEC cultures and two out of three MEC lines were productively infected by HIV-1. Virus replication significantly reduced cell proliferation, although cell viability was only slightly affected. Cytopathic changes were not observed. MEC cultures expressed low levels of surface CD4, galactosylceramide and CD26, but essentially no human leukocyte antigen (HLA)-DR. Infection of HIV-permissive MEC cells was associated with the upregulation of surface HLA-DR and CD26. In contrast, the expression of CD4, tissue-specific markers, adhesion molecules and growth-factor receptors was downregulated. To a lesser extent, similar effects were also observed in non-permissive cells. Hormones (triiodothyronine plus beta-estradiol and prolactin) enhanced HIV replication, possibly through the stimulation of cellular DNA synthesis. CONCLUSIONS: We concluded that HIV-1 replication in ductal/alveolar MEC may be, in part, responsible for the presence of HIV-1 in milk; that hormones may stimulate virus replication; and that infection reduces the growth of epithelial cells. Although in vitro HIV is produced by MEC to a lesser extent than lymphoid cells, MEC-derived HIV might have selective advantages for the infection of mucosal epithelial cells during breastfeeding.

Breast↗
PubMed1994

Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes.

To investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF-10A, negative for the expression of the P-glycoprotein, with c-Ha-ras and/or c-erbB-2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr-1 mRNA expression, the presence of P-glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF-10A transfected with both c-Ha-ras and c-erbB-2 oncogenes acquired the MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor beta 1 (TGF-beta 1): lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen.

The relationship between the expression of selected oncogenes having different modes of action and the loss of the capacity to respond in vitro to transforming growth factor-beta I (TGF-beta I) was analyzed in human mammary epithelial cells (MEC). Primary MEC cultures from healthy donors and the spontaneously immortalized MCF-10A cell line were used as normal controls. Various assays (employing both complete and chemically defined media) were used: short-term DNA synthesis, long-term cell proliferation under anchorage-dependent and -independent conditions, expression of surface-differentiation molecules. Whereas primary MEC and the MCF-10A cell line were fully responsive to the growth-inhibitory activity of TGF-beta I under different test conditions, MEC transformed by c-Ha-ras, c-erbB2, int-2, or SV40-large-T antigen were not inhibited by TGF-beta I in a short-term DNA-synthesis assay. However, in anchorage-dependent conditions TGF-beta I inhibited the proliferation of all lines investigated, with the exception of SV40-T-antigen-transformed MEC. The colony-formation assay in soft agar revealed that all lines, but not those expressing the int-2 or the SV40-T-antigen genes, were inhibited by TGF-beta I. Neutralizing antibody to TGF-beta had no significant effects on oncogene-transformed lines, suggesting that the endogenous production of an active form of this growth factor is not a major determinant in MEC transformation by the oncogenes investigated. The only observed effect of TGF-beta I on selected surface-differentiation molecules was that normal MEC produced increased levels of the human milk fat globule antigen-I. Thus it appears that the response of MEC to TGF-beta I is consistently attenuated by the insertion of a variety of oncogenes and that it is abolished only by the expression of the SV40-large-T antigen. Whereas no single in vitro assay was capable of accurately reflecting the actual responsiveness of different lines, the growth-curve assay in anchorage-dependent conditions was the best single predictive test.

Antigens, Surface↗
PubMed1994

MCF-10A cells infected with the int-2 oncogene induce angiogenesis in the chick chorioallantoic membrane and in the rat mesentery.

A growing body of evidence demonstrates the relevant role of the int-2 (FGF-3) oncogene in human carcinomas. To investigate its angiogenic activity, the human epithelial mammary cell line MCF-10A was infected with a retroviral expression vector carrying the int-2 oncogene. Infected cells were entrapped in an alginate pellet and placed on the chorioallantoic membrane of chick embryos. After 7 days, a dense capillary network was found to grow toward the pellet, whereas parental cells did not show any angiogenic activity. Conditioned medium from int-2-infected cells was injected i.p. twice daily into rats over a period of 10 days. The mesentery of treated rats showed numerous small blood vessels originating from larger vascular arcades and growing through the stromal layer of the mesentery. In control experiments, neither medium for cell culture nor conditioned medium from parental cells was found to induce angiogenesis. In conclusion, the stimulation of blood vessel growth by int-2-infected cells suggests that the production of the int-2 protein is associated with the acquisition of the angiogenic phenotype.

Allantois↗
PubMed1994

Human non-small cell lung cancer: p53 protein accumulation is an early event and persists during metastatic progression.

Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic lesions, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.

Antigens, Neoplasm↗