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C Blake Gilks

Publications and source records attributed to C Blake Gilks.

At least 37 records · Page 2Linked to original sources
PubMed2004

Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells.

Human small cell lung cancers might be derived from pulmonary cells with a neuroendocrine phenotype. They are driven to proliferate by autocrine and paracrine neuropeptide growth factor stimulation. The molecular basis of the neuroendocrine phenotype of lung carcinomas is relatively unknown. The Achaete-Scute Homologue-1 (ASH1) transcription factor is critically required for the formation of pulmonary neuroendocrine cells and is a marker for human small cell lung cancers. The Drosophila orthologues of ASH1 (Achaete and Scute) and the growth factor independence-1 (GFI1) oncoprotein (Senseless) genetically interact to inhibit Notch signaling and specify fly sensory organ development. Here, we show that GFI1, as with ASH1, is expressed in neuroendocrine lung cancer cell lines and that GFI1 in lung cancer cell lines functions as a DNA-binding transcriptional repressor protein. Forced expression of GFI1 potentiates tumor formation of small-cell lung carcinoma cells. In primary human lung cancer specimens, GFI1 expression strongly correlates with expression of ASH1, the neuroendocrine growth factor gastrin-releasing peptide, and neuroendocrine markers synaptophysin and chromogranin A (P < 0.0000001). GFI1 colocalizes with chromogranin A and calcitonin-gene-related peptide in embryonic and adult murine pulmonary neuroendocrine cells. In addition, mice with a mutation in GFI1 display abnormal development of pulmonary neuroendocrine cells, indicating that GFI1 is important for neuroendocrine differentiation.

Animals↗
PubMed2004

Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast carcinoma.

Prognostically relevant cluster groups, based on gene expression profiles, have been recently identified for breast cancers, lung cancers, and lymphoma. Our aim was to determine whether hierarchical clustering analysis of multiple immunomarkers (protein expression profiles) improves prognostication in patients with invasive breast cancer. A cohort of 438 sequential cases of invasive breast cancer with median follow-up of 15.4 years was selected for tissue microarray construction. A total of 31 biomarkers were tested by immunohistochemistry on these tissue arrays. The prognostic significance of individual markers was assessed by using Kaplan-Meier survival estimates and log-rank tests. Seventeen of 31 markers showed prognostic significance in univariate analysis (P < or = 0.05) and 4 markers showed a trend toward significance (P < or = 0.2). Unsupervised hierarchical clustering analysis was done by using these 21 immunomarkers, and this resulted in identification of three cluster groups with significant differences in clinical outcome. chi2 analysis showed that expression of 11 markers significantly correlated with membership in one of the three cluster groups. Unsupervised hierarchical clustering analysis with this set of 11 markers reproduced the same three prognostically significant cluster groups identified by using the larger set of markers. These cluster groups were of prognostic significance independent of lymph node metastasis, tumor size, and tumor grade in multivariate analysis (P=0.0001). The cluster groups were as powerful a prognostic indicator as lymph node status. This work demonstrates that hierarchical clustering of immunostaining data by using multiple markers can group breast cancers into classes with clinical relevance and is superior to the use of individual prognostic markers.

Adult↗
PubMed2004

Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma.

PURPOSE: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. EXPERIMENTAL DESIGN: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. RESULTS: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. CONCLUSIONS: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

Biomarkers, Tumor↗
PubMed2004

Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression.

Podocalyxin is a CD34-related cell surface molecule with anti-adhesive qualities. We probed a tissue microarray (n = 272) linked to long-term outcome data and found that podocalyxin was highly overexpressed in a distinct subset of invasive breast carcinomas (n = 15; 6%). Univariate disease-specific (P < 0.01) and multivariate regression (P < 0.0005) analyses indicated that this overexpression is an independent indicator of poor outcome. Forced podocalyxin expression perturbed cell junctions between MCF-7 breast carcinoma cells, and it caused cell shedding from confluent monolayers. Therefore, podocalyxin overexpression is a novel predictor of breast cancer progression that may contribute to the process by perturbing tumor cell adhesion.

Biomarkers, Tumor↗
PubMed2004

Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.

Growth factor independence-1 (GFI1) and GFI1B are closely related, yet differentially expressed transcriptional repressors with nearly identical DNA binding domains. GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation. Transgenic expression of GFI1 potentiates T-cell activation, while forced GFI1B expression decreases activation. Both mice and humans with mutant Gfi1 display lymphoid abnormalities. Here we describe autoregulation of Gfi1 in primary mouse thymocytes and a human T-cell line. GFI1 binding to cis-element sequences conserved between rat, mouse and human Gfi1 mediates direct and potent transcriptional repression. In addition, dramatic regulation of Gfi1 can also be mediated by GFI1B. These data provide the first example of a gene directly targeted by GFI1 and GFI1B. Moreover, they support a role for auto- and trans-regulation of Gfi1 by GFI1 and GFI1B in maintaining the normal expression patterns of Gfi1, and suggest that GFI1B may indirectly affect T-cell activation through repression of Gfi1.

Animals↗
PubMed2004

Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin.

Urokinase plasminogen activator (uPA) expression in breast cancer is associated with relapse and a reduction in disease-specific survival. Thus, efforts are under way to identify uPA inhibitors. By screening a chemical library of >1000 compounds, 17-allyaminogeldanamycin (17AAG) was identified as a potent inhibitor of uPA by the National Cancer Institute and is now in Phase I clinical trials. At this time, it remains unclear how 17AAG blocks uPA; one possibility is through disruption of the insulin-like growth factor I receptor (IGF-IR) pathway. This would be consistent with studies from our laboratory showing that activation of IGF-IR results in the induction of uPA protein. In the study described herein, we observed that IGF-IR and uPA were highly expressed in 87 and 55% of breast cancer by screening tumor tissue microarrays representing 930 cases. A significant proportion (52.1% = 354 of 680 cases, P < 0.0001) of the patients had tumors expressing both proteins. uPA alone (P = 0.033) or in combination with IGF-IR (P = 0.0104) was indicative of decreased disease-specific survival. Next, we demonstrated that treating MDA-MB-231 cells with increasing concentrations of 17AAG resulted in IGF-IR degradation (IC(50) = 1.0 micro M) and blocked signal transduction through the Akt and mitogen-activated protein kinase pathways. Finally, we found that 17AAG had a robust inhibitory effect on the production of uPA mRNAand protein in the presence of IGF-I. Thus, our study raises the possibility that 17AAG could prove to be an effective therapeutic agent for a large number of breast cancer patients by inhibiting the IGF-IR and ultimately uPA.

Antineoplastic Agents↗
PubMed2004

Mucinous borderline ovarian tumors: points of general agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior.

This report focuses on the borderline category of ovarian mucinous tumors and summarizes the points of general agreement and persistent controversies identified by experts in the field who participated in the Borderline Ovarian Tumor Workshop held in Bethesda, MD, in August 2003. Points of agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior are addressed for the following ovarian mucinous tumor categories: mucinous borderline ovarian tumor (M-BOT; synonymously referred to as atypical proliferative mucinous tumor of ovary or mucinous ovarian tumor of low malignant potential), M-BOT with intraepithelial carcinoma, and M-BOT with microinvasion. The morphologic spectrum of M-BOTs with regard to distinction from mucinous cystadenoma and the confluent glandular/expansile type of invasive mucinous carcinoma is also addressed. Non-ovarian mucinous tumors, including the secondary ovarian mucinous tumors associated with pseudomyxoma peritonei and metastatic mucinous carcinomas with a deceptive pattern of invasion, are recognized as tumors that can simulate primary M-BOTs. Improved classification of these mucinous tumors has clarifed the behavior of true M-BOTs by excluding these simulators from the M-BOT category.

Cystadenocarcinoma, Mucinous↗
PubMed2004

Oviductal glycoprotein, a new differentiation-based indicator present in early ovarian epithelial neoplasia and cortical inclusion cysts.

OBJECTIVE: With neoplastic progression, the precursor of epithelial ovarian cancers, the ovarian surface epithelium (OSE), undergoes Mullerian differentiation, usually of the oviductal type. The aim of this study was to examine the expression of oviduct-specific glycoprotein (OGP), a marker of normal oviductal epithelium, for use as a diagnostic or prognostic marker for ovarian cancer. METHODS AND MATERIALS: Immunohistochemical analysis for OGP was performed on 389 ovarian tumors and 19 normal ovaries, as well as 433 cases representing 45 normal tissues and 51 benign and malignant tumor types from 37 different tissues. RESULTS: OGP was absent in OSE but present in 28 of 31 epithelial inclusion cysts, 13 of 14 (93%) serous cystadenomas, and 46 of 65 (71%) serous borderline tumors. Of 183 serous adenocarcinomas, 26 (14%) were positive for OGP, including 5 of 8 (63%) grade I, 7 of 41 (17%) grade II, and 14 of 134 (10%) grade III carcinomas. OGP was found in 7 of 14 (50%) borderline and 9 of 15 (60%) malignant mucinous ovarian tumors and in 10 of 39 (26%) endometrioid adenocarcinomas. The localization of OGP in the lumen of glandular structures suggested that it was secreted. OGP was absent in 41 of 45 normal tissues and positive in oviduct and, weakly, in salivary gland, duodenum, and ileum. Forty-six types of nongynecologic tumors were negative, as were gynecologic neoplasms except for 2 of 47 cervical and 3 of 56 endometrial carcinomas. CONCLUSION: OGP is a new tubal differentiation marker which characterizes benign and borderline serous neoplasms and may indicate early events in ovarian carcinogenesis.

Adenocarcinoma↗
PubMed2004

Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level.

There is accumulating evidence that immunohistochemical staining for p53 can identify patients with endometrial carcinoma who have an adverse outcome, but the interpretation of existing data is complicated by differences between studies in the way that p53 immunohistochemistry results have been assessed. In this study, we sought to determine the appropriate cut-off level for stratification of patients with endometrial carcinoma into high- and low-risk groups, based on p53 immunohistochemical staining. A total of 200 cases of endometrial carcinoma treated by hysterectomy were retrieved from the archives of the Department of Pathology, Vancouver General Hospital, from the period 1983 to 1998. Follow-up information was available for all cases. Slides were reviewed and the diagnosis confirmed, tumors graded according to FIGO grading system, and tumor cell type assessed. A tissue microarray consisting of duplicate 0.6-mm cores of tumor was constructed and immunostained for p53. Immunoreactivity for p53 was scored by counting the number of positively stained tumor cell nuclei and expressing this as a percentage of the total number of tumor cell nuclei counted (p53 index). Kaplan-Meier survival curves were constructed and compared by calculation of log-rank statistic, and multivariate analysis was performed by Cox regression modeling. The distribution of p53 index results was bimodal, with most cases having a very low or very high p53 index. The peaks of the bimodal distribution were clearly separated using a p53 index of > or =50%. Immunoreactivity was a significant adverse prognostic indicator of disease-specific survival (p<0.0001 by univariate analysis). Patients with strongly p53 immunoreactive tumors (p53 index >or =50%) had a significantly worse outcome than patients with weakly immunoreactive (p53 index > or =5% and <50%) or p53-negative (p53 index <5%) tumors (p = 0.0001). There was no significant difference between the outcomes for patients in the latter two groups. By multivariate analysis, p53 overexpression was a significant prognostic indicator independent of patient age and tumor stage (p = 0.008) but was not independent when the analysis was extended to include FIGO grade and tumor cell type. p53 immunostaining was of prognostic significance in the subset of patients with endometrioid carcinomas (p = 0.02), but not in patients with clear cell or papillary serous carcinomas. Using a p53 index of > or =50% as a cut-off between positive and negative p53 staining, immunohistochemical staining for p53 is a prognostic indicator in patients with endometrial carcinoma of endometrioid type. p53 immunostaining was not found to be of prognostic significance independent of tumor cell type and grade.

Adult↗
PubMed2004

Early recurrence of ovarian serous borderline tumor as high-grade carcinoma: a report of two cases.

Ovarian serous borderline tumors (SBTs) are characteristically associated with an indolent course. Recurrences are often delayed and usually show morphologic features of SBT or low-grade serous carcinoma. Transformation to high-grade carcinoma has rarely been documented. We report 2 cases of ovarian SBTs that recurred early as high-grade carcinomas. The first was a 50-year-old woman treated surgically and with chemotherapy for a FIGO stage 1C SBT with microinvasion, who experienced a recurrence in an axillary lymph node at 27 months. The recurrent tumor consisted of well-differentiated papillary serous tumor that resembled the primary tumor and poorly differentiated serous carcinoma. The patient died of progressive disease 43 months after her initial presentation. The second case was a 61-year-old woman treated surgically and with chemotherapy for a stage 3C micropapillary SBT with noninvasive implants. Eighteen months later, an incisional hernia was found that contained high-grade sarcomatoid-type carcinoma with microscopic foci of better differentiated tumor that resembled the primary SBT. This patient is alive with disease 24 months after her initial presentation. Whereas the malignant potential of SBTs remains controversial, the cases described herein demonstrate that SBTs can behave unpredictably and may rarely transform into high-grade carcinoma.

Cystadenocarcinoma, Serous↗
PubMed2004

Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data.

Surface epithelial tumors are a large and heterogeneous group of neoplasms that are subclassified based on cell type and malignant potential. The objective of this review is to examine the correlations between recent molecular pathology data and the traditional histopathologic classification of surface epithelial tumors. By doing so, 6 distinct subsets of ovarian epithelial neoplasia can be identified with potential treatment implications 1. high-grade serous, high-grade endometrioid, and undifferentiated carcinomas; 2. low-grade serous carcinomas and serous borderline tumors; 3. mucinous carcinomas and mucinous borderline tumors of intestinal type; 4. low-grade endometrioid carcinomas and endometrioid borderline tumors; 5. clear cell carcinomas; and 6. transitional cell carcinomas.

Carcinoma↗
PubMed2003

Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology.

Histological diagnosis of synovial sarcoma can be difficult. Genome-wide expression profiling has identified a number of genes expressed at higher levels in synovial sarcoma than in other soft tissue tumors, representing excellent candidates for diagnostic immunohistochemical markers. A tissue microarray comprising 77 sarcomas, including 46 synovial sarcomas, was constructed to validate identified markers and investigate their expression in tumors in the differential diagnosis of synovial sarcoma. Immunostaining was performed for two such markers, epidermal growth factor receptor and SAL (drosophila)-like 2 (SALL2), and for fifteen established markers used in the differential diagnosis of sarcomas. As predicted by expression profiling, epidermal growth factor receptor (a potential therapeutic target) and SALL2 stained most cases of synovial sarcoma; staining was significantly less common among other tested sarcomas. Hierarchical clustering analysis applied to immunostaining results for all 18 antibodies showed that synovial sarcomas, leiomyosarcomas, hemangiopericytomas, and solitary fibrous tumors cluster distinctly, and assigned one case with indeterminate histology as a Ewing sarcoma. Digital images from over 2500 immunostained cores analyzed in this study were captured and are made accessible through the accompanying website: http://microarray-pubs.stanford.edu/tma_portal/synsarc.

Biomarkers↗
PubMed2003

Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFbeta genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGF beta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGF beta, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGF beta genes, respectively, was associated with elevated expression of the amplified genes.

Adult↗
PubMed2003

Tissue microarray analysis of neuroendocrine differentiation and its prognostic significance in breast cancer.

The aim of this study was to detect neuroendocrine differentiation (NE), to determine its association with major clinicopathological parameters of breast cancer, and to study the prognostic significance of NE differentiation in a group of breast carcinomas by using tissue microarray (TMA) methodology. NE differentiation was studied by using 3 markers, synaptophysin (Syn), chromogranin A (ChA), and neuron-specific enolase (NSE) in a group of 334 patients with breast carcinoma. TMA blocks were made by using duplicate 0.6-mm-diameter tissue cores from each paraffin block. Results of immunostaining were scored on a 4-point scale, that is, as negative, weak, intermediate, and strong immunoreactivity. Positive staining of breast cancers for any of the 3 NE markers was detected in 19.5% of cases. Expression of a single marker was present in 16.2% of cases, and expression of 2 or 3 markers in combination was detected in 3.3% of cases. There was no statistically significant correlation of NE phenotype with tumor morphology, except mucinous carcinoma (3 of 6 cases positive), estrogen receptor, progesterone receptor, or nodal status. A weak correlation was noted between synaptophysin staining and higher tumor grade (P = 0.029). Analysis of disease-specific and overall survival based on up to 20 years of follow-up data showed a correlation between NSE expression and improved disease-specific (P = 0.043) and overall survival (P = 0.03) in univariate but not in multivariate analysis. The expression of Syn and ChA, as well as coexpression of multiple NE markers, had no prognostic significance.

Adenocarcinoma↗
PubMed2003

Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases.

There is controversy about patient outcomes and pathological parameters of prognostic significance in patients with stage II or stage III ovarian serous borderline tumors. Forty-nine cases of stage II and III ovarian serous borderline tumors were identified on review of the medical records at Vancouver Hospital and British Columbia Cancer Agency for the period from 1979 to 1996. Pathological features assessed included presence of micropapillary architecture, tumor cell DNA content (ploidy), and characteristics of the extraovarian implants, including invasiveness and mitotic activity. Clinical follow-up information (3-17 years of follow-up) was obtained for 48 patients. Fifteen patients had stage II tumors and 34 had stage III tumors. Fourteen patients experienced tumor recurrence 1 to 8 (mean 3.5) years after presentation and of these, six patients died of disease (2, 3, 4, 7, 10, and 11 years after presentation). Patients with gross residual disease, as assessed by the surgeon, more frequently experienced a recurrence compared with patients without gross residual disease, but this difference did not reach statistical significance (0.05<p<0.1). The patients who died of disease all had stage III tumors. Patients with invasive implants had a significantly worse outcome than patients with noninvasive implants (p<0.005). Other pathological features (ploidy, micropapillary architecture, invasiveness of implants, mitotic activity of implants) were not significantly predictive of tumor recurrence or death. No single pathological feature or combination of features was present in all patients who subsequently died of disease. In conclusion, the prognosis for patients with advanced-stage serous borderline tumors in this population-based study is very favorable, with only six patients ultimately dying of progressive disease. The combination of stage (stage III) and invasiveness of extraovarian implants identifies a small subset of patients with advanced-stage serous borderline tumors with a significantly worse prognosis, who may benefit from adjuvant therapy.

Combined Modality Therapy↗
PubMed2002

Software tools for high-throughput analysis and archiving of immunohistochemistry staining data obtained with tissue microarrays.

The creation of tissue microarrays (TMAs) allows for the rapid immunohistochemical analysis of thousands of tissue samples, with numerous different antibodies per sample. This technical development has created a need for tools to aid in the analysis and archival storage of the large amounts of data generated. We have developed a comprehensive system for high-throughput analysis and storage of TMA immunostaining data, using a combination of commercially available systems and novel software applications developed in our laboratory specifically for this purpose. Staining results are recorded directly into an Excel worksheet and are reformatted by a novel program (TMA-Deconvoluter) into a format suitable for hierarchical clustering analysis or other statistical analysis. Hierarchical clustering analysis is a powerful means of assessing relatedness within groups of tumors, based on their immunostaining with a panel of antibodies. Other analyses, such as generation of survival curves, construction of Cox regression models, or assessment of intra- or interobserver variation, can also be done readily on the reformatted data. Finally, the immunoprofile of a specific case can be rapidly retrieved from the archives and reviewed through the use of Stainfinder, a novel web-based program that creates a direct link between the clustered data and a digital image database. An on-line demonstration of this system is available at http://genome-www.stanford.edu/TMA/explore.shtml.

Cluster Analysis↗
PubMed2002

Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.

On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with low-grade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P =.004 and P =.018, respectively), and both were strongly correlated with p53 expression (P =.01 and P =.006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome.

Adenocarcinoma, Papillary↗