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Biomedical subjects

David S Alberts

Publications and source records attributed to David S Alberts.

At least 73 records · Page 4Linked to original sources
PubMed2003

Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.

PURPOSE: Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response. EXPERIMENTAL DESIGN: Healthy participants with Fitzpatric skin type II or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea polyphenol treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products. There was a >60% increase in the area under the plasma EGCG concentration-time curve after 4 weeks of green tea polyphenol treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of EGCG after repeated green tea polyphenol treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of epigallocatechin and epicatechin were not affected by repeated green tea polyphenol treatment. Four weeks of green tea polyphenol treatment at the selected dose and dosing schedule did not provide protection against UV-induced erythema. CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily).

Adult↗
PubMed2003

Association between Cyclooxygenase expression and colorectal adenoma characteristics.

The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined. Accordingly, we analyzed 108 colorectal adenomas for COX-1 and COX-2 transcription in archival formalin-fixed, paraffin-embedded tissue using by real-time PCR and normalized to beta-actin. Neither COX-1 nor COX-2 mRNA expression differed with regard to age or gender of the subject. COX-2 mRNA expression was significantly higher in distal adenomas (2.2 +/- 1.9) compared with proximal (0.7 +/- 0.5) adenomas (P < 0.0001) and in larger (>/=7 mm) compared with smaller (<7 mm) adenomas (2.3 +/- 2.2 and 1.7 +/- 1.3, respectively, P = 0.04). COX-2 expression did not differ significantly in tubular compared with tubulovillous adenomas, although there appeared to be a trend toward higher COX-2 expression in tubulovillous adenomas with increasing villous content. Additionally, there was not a significant difference in either COX-1 or COX-2 based on the degree of dysplasia Therefore, if COX-2 inhibitors work through a COX-2 mechanism, these agents may have differential effects on colorectal adenomas that are distal and larger.

Adenoma↗
PubMed2003

Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene.

Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between two myc-binding domains. This region is known to affect ODC transcription, but no data exist on the relationship of this polymorphism to risk of colorectal neoplasia in humans. We show that individuals homozygous for the minor ODC A-allele who reported using aspirin are approximately 0.10 times as likely to have an adenoma recurrence as non-aspirin users homozygous for the major G-allele. Mad1 selectively suppressed the activity of the ODC promoter containing the A-allele, but not the G-allele, in a human colon cancer-derived cell line (HT29). Aspirin (>or=10 microM) did not affect ODC allele-specific promoter activity but did activate polyamine catabolism and lower polyamine content in HT29 cells. We propose that the ODC polymorphism and aspirin act independently to reduce the risk of adenoma recurrence by suppressing synthesis and activating catabolism, respectively, of colonic mucosal polyamines. These findings confirm the hypothesis that the ODC polymorphism is a genetic marker for colon cancer risk, and support the use of ODC inhibitors and aspirin, or other nonsteroidal antiinflammatory drugs (NSAIDs), in combination as a strategy for colon cancer prevention.

Adenoma↗
PubMed2003

Combined intraperitoneal and intravenous chemotherapy for women with optimally debulked ovarian cancer: results from an intergroup phase II trial.

PURPOSE: The median survival time for women with optimally debulked adenocarcinoma of the ovary treated with intravenous (IV) chemotherapy is 41 to 52 months, and the 2-year survival rate is 65% to 70%. Recent studies evaluating intraperitoneal (IP) chemotherapy have reported a median survival time of 49 to 63 months and 2-year survival rates of 70% to 80%. This phase II trial was undertaken to evaluate the feasibility of and 2-year survival rate achieved by the combination of IP paclitaxel, IP cisplatin, and IV paclitaxel in women with optimally debulked, stage III ovarian cancer. PATIENTS AND METHODS: Treatment consisted of paclitaxel 135 mg/m(2) IV over 24 hours on days 1 to 2, cisplatin 100 mg/m(2) IP on day 2, and paclitaxel 60 mg/m(2) IP on day 8 administered every 21 days for six cycles. RESULTS: In 68 assessable women with optimal stage III ovarian cancer, the 2-year survival rate was 91%, and the median survival time was 51 months. The 2-year disease-free survival rate was 66%, and median disease-free survival time was 33 months. Ninety-six percent of all patients experienced at least one grade 3 to 4 adverse event during therapy, with the most common events being neutropenia (79%), nausea (50%), vomiting (34%), and fatigue/malaise/lethargy (24%). Seventy-one percent of patients completed all six cycles of IV/IP therapy as planned. CONCLUSION: Combined IV and IP chemotherapy with cisplatin and paclitaxel is associated with a very promising 2-year survival rate in women with optimally debulked ovarian cancer. The ultimate impact of this approach on overall survival requires further evaluation in a randomized trial setting.

Adenocarcinoma↗
PubMed2003

Variation in cyclooxygenase expression levels within the colorectum.

The positive association of decreased risk of colorectal cancer with nonsteroidal antiinflammatory drug (NSAID) use, combined with the observation that cyclooxygenase(COX)-2 is present in a majority of colorectal tumors, has led to the proposed use of isozyme-specific COX inhibitors as preventive agents in polyp and tumor formation in the colon. However, the exact biochemical mechanisms and disease stage at which reduced risk is mediated remain somewhat controversial, in part because of the complex biochemical changes that occur during the progression from aberrant crypt to polyp to tumor. In this study, COX-1 and COX-2 protein expression levels were determined in sets of tumor and normal colon tissue. Changes were characterized in COX-1 and COX-2 expression within individuals, in relation to such factors as sex, tumor grade, and location in the colorectum. COX-1 expression levels were found to be significantly reduced in tumors compared to matched normal tissues (Dunn's method, P < 0.05). Additionally, COX-1 expression was decreased in stage T3 tumors as compared to stage T2 tumors (Student's t-test, P = 0.009). Similar to previous reports, COX-2 protein expression was present in 73% of the tumors studied and appeared to be independent of tumor grade and sex. Interestingly, decreased COX-2 expression correlated with tumor occurrence in rectal mucosa (Wilcoxon two-sample test, P < 0.05). These results warrant further investigation, especially the identification of determinants that would predict which populations would be most responsive to COX-2 inhibition as a means of colorectal cancer chemoprevention.

Colon↗
PubMed2003

Assay-assisted treatment selection for women with breast or ovarian cancer.

Although women suffering from advanced cancer of the breast or ovary are unlikely to be cured, several active agents are available that can prolong their lives. The use of these agents is based on demonstrated benefit in large randomized clinical trials, and the clinical activity of these chemotherapy regimens is initially high, with 60%-70% of patients responding. Unfortunately, their benefit in the second-line setting is often limited, with less than 30% of patients showing significant disease response. Thus some 70% of patients may undergo ineffective treatment during the course of their disease, while still suffering from significant chemotherapy-related toxicity. Having some foreknowledge of a given agent's expected result before its administration would therefore benefit the individual patient. In vitro drug response testing, first developed to assist in the selection of antibiotics for patients with bacterial infections, has recently been demonstrated to accurately predict how cancer patients will respond to chemotherapy. This review discusses the historical development of in vitro testing for cancer patients, some of the pitfalls encountered, and offers an assessment of their current utility. Results of various clinical trials that evaluated correlations between in vitro tumor response and clinical outcomes are described. These data suggest that in vitro drug response assays can accurately predict drug resistance and can identify patients who are more or less likely to benefit from a given agent.

Antineoplastic Agents↗
PubMed2003

Skin cancer chemoprevention: strategies to save our skin.

There are over 1 million cases of skin cancer diagnosed yearly in the United States. The majority of these are nonmelanoma (NMSCs) and are associated with chronic exposure to ultraviolet light (UV). Actinic keratosis (AK) has been identified as a precursor for SCC, but not for BCC. AKs are far more common than SCC, making them excellent targets for chemoprevention. Cancer chemoprevention can prevent or delay the occurrence of cancer in high-risk populations using dietary or chemical interventions. We have developed strategies that have rational mechanisms of action and demonstrate activity in preclinical models of skin cancer. Promising agents proceed to phase I-III trials in subjects at high risk of skin cancer. UV light induces molecular signaling pathways and results in specific genetic alterations (i.e., mutation of p53) that are likely critical to skin cancer development. UVB-induced changes serve as a basis for the development of novel agents. Targets include inhibition of polyamine or prostaglandin synthesis, specific retinoid receptors, and components of the Ras and MAP kinase signaling pathways. Agents under study include: epigallocatechin gallate (EGCG), a green tea catechin with antioxidant and sunscreen activity, as well as UVB signal transduction blocking activity; perillyl alcohol, a monoterpene derived from citrus peel that inhibits Ras farnesylation; difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase and polyamines; retinoids that target retinoid X receptors and AP-1 activity; and nonsteroidal anti-inflammatory agents that inhibit cylooxygenase and prostaglandin synthesis. We performed a series of Phase I-II trials in subjects with multiple AK. For example, a phase II randomized trial of topical DFMO reduced AK number, suppressed polyamines, and reduced p53 protein. Our goal is to develop agents for use in combination and/or incorporation into sunscreens to improve chemoprevention efficacy and reduce skin cancer incidence.

Animals↗
PubMed2003

Nutrition and diet in the development of gastrointestinal cancer.

Diet plays a role in the prevention and development of gastrointestinal cancers. The majority of available research consists of case-control studies, but the number of clinical trials is growing. The dietary recommendations to reduce gastrointestinal cancer risk include lowering total energy, fat, and saturated fat intake; avoidance of grilled and smoked foods; avoidance of alcohol; and increasing intake of fruits, vegetables, and fiber. Studies of esophageal cancer support these dietary approaches, with the exception of dietary fat reduction and increased green tea intake. For gastric cancer, consuming additional fruits and vegetables, including those high in ascorbic acid, may reduce risk, and the capacity for diet to alter Helicobacter pylori infection should be explored. Recent interventional trials do not support a role for high-fiber or low-fat diets in reducing development of colon adenomas, although the evidence does not rule out efficacy at earlier stages of disease. Finally, the evidence for a relationship between pancreatic cancer and diet remains sparse and warrants additional investigation.

Diet↗
PubMed2003

Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival.

Thioredoxin-1 is a redox protein that, when overexpressed, causes increased cancer-cell growth and inhibited apoptosis. Thioredoxin-1 expression has been reported to be increased in several human primary tumors, but its relationship to tumor progression and patient survival has not been established. We studied the expression of thioredoxin-1 as measured with immunohistochemical staining in paraffin-embedded human normal colonic mucosa, adenomatous polyps, and primary and metastatic colorectal cancer. Thioredoxin-1 expression was not increased in 12 colorectal adenomatous polyps, compared with 8 samples of normal colonic mucosa, but was significantly increased in 12 primary colorectal cancers (P <.01). Thioredoxin-1 expression was not significantly different in primary lymph-node metastases and the primary colorectal cancer. Using colorectal cancer samples from 37 subjects for whom survival data was available, we found that thioredoxin-1 expression increased with Dukes stage, although the association was not statistically significant (P =.077). We noted a significant association between thioredoxin-1 expression and patient survival (P =.004); higher score was associated with decreased survival. When adjusted for Dukes stage, thioredoxin-1 expression showed a statistically significant association with survival (P =.012). The work shows that increased thioredoxin-1 expression is a relatively late event in colorectal carcinogenesis and provides evidence in a small group of subjects with colorectal cancer of Dukes stages A through D that thioredoxin-1 expression may be an independent marker of patient prognosis.

Adult↗
PubMed2003

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial.

OBJECTIVE: To improve the survival of women with stage IV epithelial ovarian cancer the Southwest Oncology Group conducted a phase II trial examining two novel treatment strategies: (a) modification of the chemotherapy regimen (carboplatin/paclitaxel) based on evidence of response during treatment and (b) "maintenance therapy," with the monthly administration of single agent paclitaxel (maximum 2 years). METHODS: Individuals with histologically documented stage IV ovarian, fallopian tube, or peritoneal cancers initially received a maximum of 3 courses of single agent carboplatin (AUC 6), with the decision to administer a subsequent course based on specific response criteria (i.e., declines in serum CA-125 or shrinkage of measurable mass lesions). This was followed by single agent paclitaxel (150 mg/m(2)), delivered every 2 weeks for a maximum of 6 courses, again based on evidence of continued response to the treatment program. Finally, in the absence of disease progression or unacceptable toxicity, patients received single agent paclitaxel (175 mg/m2) for a maximum of 24 monthly courses. The primary study end point was 2-year overall survival, which was to be compared to the survival of a previously published historical control population [stage IV ovarian cancer patients treated with a "standard" cisplatin/paclitaxel regimen (GOG 111; McGuire WP, N Eng E J Med 1996; 334:1)]. This analysis was employed to determine if this novel strategy was worthy of further clinical investigation in a controlled clinical trial. RESULTS: There were 53 patients entered this multicenter study, of whom 50 were evaluable for toxicity and 51 for survival. There were 2 treatment-related deaths. Grades 2 and 3 neutrotoxicity were observed in 18 and 4% of patients, respectively. There were no major treatment-related protocol violations. The overall 2-year survival was 48% (95% CI, 34-62%), compared to 60% for the historical control group. CONCLUSIONS: While this trial demonstrated the feasibility of delivering a treatment regimen requiring frequent alternations in therapy based on predetermined changes in objective parameters of response, further exploration of this specific management approach does not appear warranted in stage IV ovarian cancer, based on the survival outcome compared to a reasonably similar historical control population. As this trial demonstrates, the prospective determination of clinical end points in a phase II study (e.g., 2-year survival) that will lead to continued evaluation of a particular investigative strategy in a large-scale randomized trial can be an effective method to reduce the bias and uncertainty often associated with this complex decision process.

Adult↗
PubMed2003

Amifostine pretreatment for protection against topotecan-induced hematologic toxicity: results of a multicenter phase III trial in patients with advanced gynecologic malignancies.

OBJECTIVE: To determine if amifostine could reduce the hematologic toxicity associated with topotecan. METHODS: Thirty patients with recurrent/refractory gynecologic malignancies were randomized to receive topotecan (TOPO) (1.5 mg/m(2)/day days 1-5) with or without amifostine (AMI/TOPO) (500 mg/m(2)/day days 1-5) every 3 weeks for six cycles. The primary study endpoints were the incidence of grade 3 and 4 neutropenia. RESULTS: Fifteen patients were randomized to each arm for a total of 49 TOPO and 53 AMI/TOPO cycles. Patient characteristics and pretreatment ANC were similar between groups. Topotecan 1.5 mg/m(2)/day days 1-5 was initially administered to seven patients. Five developed neutropenic fevers, one an uncomplicated grade 4 neutropenia, and the other an uncomplicated grade 3 neutropenia. There were two treatment-related deaths due to sepsis (one in each treatment arm). The starting dose was thereafter reduced to 1.25 mg/m(2)/day days 1-5 every 21 days. No treatment related deaths occurred after this dose reduction. The incidence of combined grade 3/4 neutropenia was reduced from 67% (33/49 cycles) to 38% (20/53 cycles) with the addition of amifostine (P = 0.003; OR 0.29; 95% CI 0.12-0.71). CONCLUSIONS: Topotecan at 1.5 mg/m(2)/day days 1-5 in heavily pretreated patients resulted in excessive toxicity not manageable with amifostine. At the reduced topotecan dose (1.25 mg/m(2) x 5 days), pretreatment with amifostine reduced the hematologic toxicity associated with topotecan chemotherapy in women with recurrent/refractory gynecologic malignancies.

Adult↗
PubMed2003

Adenoma recurrences after resection of colorectal carcinoma: results from the Southwest Oncology Group 9041 calcium chemoprevention pilot study.

BACKGROUND: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC). METHODS: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates. RESULTS: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates. CONCLUSIONS: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.

Adenoma↗
PubMed2003

Fecal bile acid concentrations in a subpopulation of the wheat bran fiber colon polyp trial.

Factors that affect the concentration of secondary bile acids in the aqueous phase of stool may have a greater impact on colon carcinogenesis than those that only modify the total fecal bile acid concentration. This hypothesis was tested using stool samples of a subset of participants enrolled in a Phase III colorectal adenomatous polyp prevention trial, which documented the inability of a 13.5 g/day wheat bran fiber (WBF) supplement to reduce polyp recurrence. Stool was collected from 68 consecutively consented participants who were enrolled in a Phase III clinical trial of WBF for the prevention of adenomatous polyp recurrence. Nineteen (27.9%) of these fecal bile acid substudy participants were on the low fiber (2.0 g/day) intervention group, whereas 49 (72.7%) were on the high fiber (13.5 g/day) intervention group for approximately 3 years. Sixty-four participants had both the aqueous and solid phases of stool samples analyzed for bile acid content. Bile acid concentrations, measured in microg/ml for fecal water and microg/mg for dry feces, were determined for lithochilic, deoxycholic, chenodeoxycholic, cholic, ursodeoxycholic, isodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids. There were no significant differences between the low and high fiber groups concerning mean or median aqueous phase concentrations of lithocholic or deoxycholic bile acids. In contrast, the median concentrations of deoxycholic acid and other secondary bile acids (including lithochilic, isodeoxycholic, ursodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids) were significantly lower for the high fiber group in the solid-phase stool (P < 0.05). These results document that a high WBF intervention, taken for a median of 2.4 years, does not significantly reduce aqueous-phase concentrations of secondary bile acids in stool, although their concentrations in solid-phase stool were suppressed. Thus, the inability of the high WBF intervention to reduce colorectal adenoma recurrence may be a consequence of its lack of effect on fecal aqueous-phase secondary bile acid concentrations.

Adenomatous Polyposis Coli↗
PubMed2003

Malignancy-associated changes in lactiferous duct epithelium.

OBJECTIVE: To determine whether cells from histologically normal appearing epithelium of the lactiferous duct from women with a remote ductal lesion in the breast provide any clues indicating the existence of such a lesion. STUDY DESIGN: Tissue sections cut to 4 microns and stained with hematoxylin and eosin were prepared from duct tissue of 20 women with breast lesions and of 20 women free of any such lesion who had undergone mammoplastic procedures or resection for benign reasons. One hundred nuclei were measured from each case. Measures of nuclear deviation from normal were computed, discriminant functions were derived, and multivariate significance tests were conducted. RESULTS: Nuclei from histologically normal appearing regions of lactiferous duct epithelium from women harboring distant lesions exhibited changes in the distribution pattern of their nuclear chromatin, indicating the presence of these lesions. The statistical significance of these changes was documented. The changes were clearly evident in all 20 subjects with lesions and were not observed in 19 of the 20 subjects without lesions. CONCLUSION: The results suggest that studies aimed at detecting malignancy-associated changes in cells collected by ductal lavage might lead to a minimally invasive screening procedure for breast lesions.

Adult↗
PubMed2003

Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies.

OBJECTIVE: To develop a reliable and valid scoring system for grading skin biopsies from actinic keratosis (AK) and sun-damaged skin for use in evaluating the efficacy of skin cancer chemopreventive agents. STUDY DESIGN: A panel of dermatopathologists developed histologic criteria and diagnostic definitions for the progression of lesions from early AK to AK. The criteria were then applied to a sample of 335 histologic slides from an ongoing chemoprevention study. A 10% sample of 35 slides was reread in order to assess intrarater reliability. RESULTS: Six of the 7 criteria demonstrated high reliability (> 85%). The total histologic score, calculated using the 6 criteria, was found to significantly differentiate between (blinded) biopsy location (normal, pre-AK, AK and adjacent to squamous cell carcinoma) and histologic diagnosis (normal, pre- or early AK, AK and squamous cell carcinoma). CONCLUSION: The total histologic score, having demonstrated reliability on repeated readings and validity in its association with biopsy location and histologic score, is a reliable and valid end point for judging the efficacy of agents in skin cancer chemoprevention studies. Additional interrater reliability tests utilizing larger test sets and a rigorous statistical design should be undertaken to establish its portability.

Biopsy↗
PubMed2003

A karyometric approach to the characterization of atypical endometrial hyperplasia with and without co-occurring adenocarcinoma.

OBJECTIVE: To develop a karyometric image analysis approach to distinguishing atypical endometrial hyperplasia with and without co-occurring adenocarcinoma. STUDY DESIGN: Six cases of atypical hyperplasia without and 6 cases with co-occurring adenocarcinoma, 4 cases of normal endometrium and 3 cases of adenocarcinoma were identified. From each case 100 nuclei were measured in representative diagnostic areas identified by an experienced pathologist. Discriminant analyses were performed. An unsupervised learning algorithm was applied to define and characterize different nuclear phenotypes, and those data were used to identify cases with co-occurring adenocarcinoma. RESULTS: Discriminant analysis showed that nuclei from atypical hyperplasia and atypical hyperplasia with co-occurring adenocarcinoma are statistically different. The unsupervised learning algorithm revealed differences in nuclear subpopulations that can be used to correctly identify an estimated 85% of individual cases. CONCLUSION: Nuclei from atypical hyperplasia without and with co-occurring adenocarcinoma have statistically different karyometric characteristics that may facilitate case classification.

Adenocarcinoma↗