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Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay.

INTRODUCTION: Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation. METHODS: Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and qRT-PCR data by hierarchical clustering. A proliferation signature was used as a single meta-gene (log2 average of 14 genes) to predict outcome within the context of estrogen receptor status and biological 'intrinsic' subtype. RESULTS: We found that the qRT-PCR assay could determine the intrinsic subtype (93% concordance with microarray-based assignments) and that the intrinsic subtypes were predictive of outcome. The proliferation meta-gene provided additional prognostic information for patients with the Luminal subtype (P = 0.0012), and for patients with estrogen receptor-positive tumors (P = 3.4 x 10-6). High proliferation in the Luminal subtype conferred a 19-fold relative risk of relapse (confidence interval = 95%) compared with Luminal tumors with low proliferation. CONCLUSION: A real-time qRT-PCR assay can recapitulate microarray classifications of breast cancer and can risk-stratify patients using the intrinsic subtype and proliferation. The proliferation meta-gene offers an objective and quantitative measurement for grade and adds significant prognostic information to the biological subtypes.

Breast Neoplasms↗

[Prostate cancer diagnosis using ultrasound elastography. Introduction of a novel technique and first clinical results].

During the last decade screening has improved prostate cancer detection. The main reason for this development is a better understanding of the margins of prostate-specific antigen (PSA) serum levels and the classification of PSA subtypes. In contrast, the introduction of transrectal ultrasound has not led to a measurable change in the prostate cancer detection rate. Our aim was to develop a novel ultrasound system for the acquisition of elastographic images of the prostate and evaluate the system regarding its clinical applicability. We used a technically modified conventional ultrasound system and analyzed the high-frequency ultrasonic data with a computer program. The first patient-based results suggest that elastography allows an accurate measurement of tumor size and localization in contrast to conventional transrectal ultrasound. Elastography visualizes different tissue elasticities to distinguish benign and cancerous tissue. Thus, we were able to even correctly classify prostate cancer lesions which are iso- or hyperechoic in B-mode sonography.

Aged↗

[New WHO classification of lymphoid neoplasms: understanding and consideration].

The latest version of new WHO classification of lymphoid neoplasms is a comprehensive and distinct opinion of lymphoid neoplasms, and maybe put an end to the controversy held in this field for a long time. The new classification defines the neoplasm categories according to the principle that the classification should be based on the real entities of diseases and should contain the morphology, immunophenotypes, genetic alterations and clinical features rather than simply emphasize the pure morphologic presentations. The new subtyping of lymphoid cancers provides a correct framework for malignant lymphoma, and also represents a new paradigm in disease classification. So far the accumulated experiences have demonstrated that the new classification is reproducible and practical. However, it remains to determine how the variants of lymphomas relate to their clinical prognostic factors, such as international prognostic index and individual difference, since the current treatment approach relays on the types of lymphomas. The diagnosis, treatment and researches of lymphomas in China are also discussed.

Humans↗

Classification and clinical course of low-grade non-Hodgkin's lymphomas with overview of therapy.

Low-grade non-Hodgkin's lymphoma (NHL) presents a formidable treatment challenge to oncologists. This review evaluates the various methods of disease and patient management. The natural history of various subtypes of low-grade NHL and the classification according to the National Cancer Institute Working Formulation are discussed in this review. Additionally, the various therapies in use; radiotherapy alone and combined with chemotherapy, chemotherapy with single alkylating agents such as chlorambucil and combination therapies, autologous and allogenic bone marrow transplantation, and therapy with purine analogs, such as chlorodeoxyadenosine and fludarabine. Patient survival in various studies using these treatment modalities are discussed. Treatment options need to be combined with the use of prognostic models, such as the International Index for optimal care of this difficult-to-treat group of patients.

Humans↗

In search of a stem cell hierarchy in the human breast and its relevance to breast cancer evolution.

By deliberate analogy with the well-established concept of hematopoiesis, the term "mammopoiesis" is occasionally used to describe the development of the different cellular lineages and functional units in the mammary gland. The use of this term signifies a strong bias towards the idea that tissue homeostasis during mammary development, pregnancy, lactation and involution is brought about by the action of somatic stem cells characterized by longevity and multipotency. The progenies hereof eventually differentiate into structurally and functionally well-defined ductal-lobular units. During the past two decades evidence of such a notion in the mouse has developed from being largely circumstantial based on non-clonal in vivo experiments to a quite elaborate characterization of individual candidate stem cells by a number of different properties. Within tumor biology this has led to a renaissance of the concept of tumors as caricatures of tissue renewal. Thus, recent molecular classification of breast cancer based on genome wide expression analysis operates with different subtypes with specific reference to the normal luminal epithelial and myoepithelial/basal lineages in the breast. Apparently some tumors are lineage restricted and others differentiate more broadly as if they have preserved some stem-like properties. This holds promise for the existence of a stem cell hierarchy, the understanding of which may prove to be instrumental in further dissecting the histogenesis of breast cancer evolution. Most attention has been devoted to the question of different cellular origins of cancer subtypes and different susceptibilities of possible stem cells to gain or loss of oncogenes and tumor suppressor genes, respectively. Invaluable progress has been made over the past two decades in culture technology not only in terms of population doubling and clonal growth, but also the availability of lineage specific markers, cell sorting, and three-dimensional functional assays for tissue specific morphogenesis. Transcriptional profiling of stem cell zones has unraveled a hitherto unknown preservation of signaling pathways for maintenance of stem cell properties across tissue boundaries and species. Somatic stem cells have therefore been narrowed down to specific anatomic locations not only in rapidly renewing tissues such as skin and skin derivatives, but also in tissues with slower turnover times, such as lung, kidney and prostate. It is therefore now possible to integrate this information in a search for similar cells within the breast. Even if cell turnover after birth is provided exclusively by dividing lineage-restricted cells, more information about the robustness of breast differentiation programs during tumor progression is still very much required. Complete knowledge of the primary cell of origin of breast cancer and the mechanisms that influence differentiation programs during tumor initiation, promotion and progression may be crucial for the development of novel non-toxic therapies that influence tumor cell behaviour. The scope of this review is to discuss reports that have begun to elucidate the topographic location, key cellular type and lineage fidelity in culture and xenograft models of candidate human breast stem cells and their differentiated progenies with particular emphasis on comparison with the differentiation programs of tumor subtypes.

Animals↗

The rationale for standardized registration and reporting of brain and central nervous system tumors in population-based cancer registries.

Most population-based statistical reports of brain and central nervous system (CNS) tumors are limited to data of primary malignant tumors and to summary estimates of all tumor locations and histologies. We argue that data of benign brain and CNS tumors should also be included in registry reports and that standard definitions for the reporting of all brain and CNS tumors by site and histology should exist. We demonstrate current inconsistencies in the definitions of brain and CNS tumor sites used in reports. Grouping of brain and CNS tumors by subtype--which integrates the current World Health Organization classification scheme with the International Classification of Diseases for Oncology coding system used in cancer registries--is proposed. Adoption of standard tumor site and behavior codes for annual reports would aid the comparison of rates of brain and CNS tumors between geographic regions, allow for the evaluation of trends over time, and provide new estimates of tumor subtypes in a more clinically relevant format. A consensus among cancer registries and neuroscientists is needed to adopt standard definitions so that accurate and clinically relevant brain and CNS tumor data are available.

Behavior↗

[Histopathological analysis of gastric polyps: classification and relationship to cancer].

34 cases of gastric polyps were investigated histopathologically. Based on Nakamura's classification, hyperplastic polyps were further classified into the following subtypes: the foveolar epithelial type, fundic glandular hyperplastic type and pyloric glandular hyperplastic type, each being described in detail. It was found that atypical hyperplastic foci usually appear in the foveolar epithelial subtype, indicating a close relationship to cancer. This finding suggests that the subclassification of hyperplastic gastric polyp has a higher practical value in clinical application. The article has also presented a histochemical and CEA immunohistochemical comparative study between hyperplastic polyps, adenoma and atypical hyperplasia of the stomach. The malignant transformation of gastric polyps is discussed and the definition of polyp reconsidered.

Adenoma↗

[An extended operation for scirrhous gastric cancer--its significance and procedure].

We have been performing an extended operation for scirrhous gastric cancer, namely left upper abdominal exenteration plus Appleby's method, and compared the prognosis among macroscopic subtype classifications. The surgical procedure of left upper abdominal exenteration plus Appleby's method is to resect the neighboring organs of the stomach in an en bloc fashion. It consists of total gastrectomy, partial pancreatectomy, splenectomy, transverse colectomy, cholecystectomy, resection of the left adrenal gland, and ligation and resection of the common hepatic artery. D4 lymph node dissection is carried out. Extended operations were performed for 45 cases of P0-1 scirrhous gastric cancer in 1983-1990. There were 25, 17 and 3 cases of giant fold type, erosive type and stenotic type scirrhous gastric cancers, respectively. Positive lymph node metastases were found in 64% of giant fold type cases and 82% of erosive type cases. In Po, T3-4 cases, cytology of intraoperative peritoneal lavage was positive in 27% of giant fold type cases and 50% of erosive type cases. Although there were no obvious macroscopic invasions found during the operative procedure, later histological study showed invasion to the left adrenal gland in 14% of giant fold type cases and 0% of erosive type cases, and invasion to the transverse colon in 21% of giant fold type cases and 15% of fold type and erosive type scirrhous gastric cancer according to the histological invasion of transverse colon were 25% in positive cases and 27% in negative cases (p = 0.27), 0% in positive cases and 27% in negative cases (p = 0.27), respectively. In giant fold type scirrhous gastric cancer, the extended operation is favorable. In erosive type scirrhous gastric cancer, peritoneal dissemination is observed with a high incidence. Therefore, prophylactic therapy is significant.

Adenocarcinoma, Scirrhous↗

A working group classification of focal prostate atrophy lesions.

Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of "training" images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct "test" images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of "standard" diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the "training set" of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.

Atrophy↗

Detection of large cell component in small cell lung carcinoma by combined cytologic and histologic examinations and its clinical implication.

BACKGROUND: In the classification recently proposed by the Pathology Committee of International Association for the Study of Lung Cancer, small cell lung carcinoma (SCLC) was divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. METHODS: To examine the clinical utility of this classification, histologic specimens, cytologic specimens obtained by brushing or fine-needle aspiration, and sputum cytologic specimens from 430 patients with SCLC were reviewed. RESULTS: When the subtype of SCLC was determined from the biopsy specimen, cytologic specimen obtained by brushing or fine-needle aspiration, and sputum cytologic specimen, the frequency of mixed SC/LC was 25 of 299 (8.4%), 75 of 400 (18.8%), and 8 of 232 (3.4%), respectively. Whatever the diagnostic method, patients with mixed SC/LC showed a poorer response to treatment and worse prognosis than those with pure SCLC: a median survival of 144 days versus 285 days when classified with the use of biopsy specimens; 160 days versus 275 days with cytologic specimens obtained by brushing or fine-needle aspiration; and 47 days versus 259 days with sputum cytologic specimens, respectively. CONCLUSIONS: These findings showed that mixed SC/LC should be separated from pure SCLC as a distinctive group and that cytologic studies of specimens obtained by brushing or fine-needle aspiration were sensitive and useful procedures for this purpose.

Adult↗

[The influence of smoking on the development of various subtypes of pulmonary carcinoma].

The influence of smoking on the development of pulmonary carcinoma of various histological subtypes was analyzed in 244 primary and 84 metastatic lung cancer patients. The new WHO classification was used for histological diagnosis. The relative risk was calculated by the odds ratio. It was found that all the squamous, small-and large-cell carcinomas were derived from smokers with relative risks of 27.8, 7.5 and 5.6, respectively. On the other hand, adenocarcinoma had very little, if any, relationship with smoking, the relative risk being 1.5 in men and 1.3 in women. The high-risk group for squamous cell carcinoma in men was defined with a regression line of y (duration of smoking) on x (number of cigarettes per day) as y = -0.24 x + 48.6.

Adenocarcinoma↗

Automated Classification of Lymphoma Subtypes From Histopathological Images Using a U-Net Deep Learning Model: Comparative Evaluation Study.

BACKGROUND: Accurate classification and grading of lymphoma subtypes are essential for treatment planning. Traditional diagnostic methods face challenges of subjectivity and inefficiency, highlighting the need for automated solutions based on deep learning techniques. OBJECTIVE: This study aimed to investigate the application of deep learning technology, specifically the U-Net model, in classifying and grading lymphoma subtypes to enhance diagnostic precision and efficiency. METHODS: In this study, the U-Net model was used as the primary tool for image segmentation integrated with attention mechanisms and residual networks for feature extraction and classification. A total of 620 high-quality histopathological images representing 3 major lymphoma subtypes were collected from The Cancer Genome Atlas and the Cancer Imaging Archive. All images underwent standardized preprocessing, including Gaussian filtering for noise reduction, histogram equalization, and normalization. Data augmentation techniques such as rotation, flipping, and scaling were applied to improve the model's generalization capability. The dataset was divided into training (70%), validation (15%), and test (15%) subsets. Five-fold cross-validation was used to assess model robustness. Performance was benchmarked against mainstream convolutional neural network architectures, including fully convolutional network, SegNet, and DeepLabv3+. RESULTS: The U-Net model achieved high segmentation accuracy, effectively delineating lesion regions and improving the quality of input for classification and grading. The incorporation of attention mechanisms further improved the model's ability to extract key features, whereas the residual structure of the residual network enhanced classification accuracy for complex images. In the test set (N=1250), the proposed fusion model achieved an accuracy of 92% (1150/1250), a sensitivity of 91.04% (1138/1250), a specificity of 89.04% (1113/1250), and an F1-score of 90% (1125/1250) for the classification of the 3 lymphoma subtypes, with an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97). The high sensitivity and specificity of the model indicate strong clinical applicability, particularly as an assistive diagnostic tool. CONCLUSIONS: Deep learning techniques based on the U-Net architecture offer considerable advantages in the automated classification and grading of lymphoma subtypes. The proposed model significantly improved diagnostic accuracy and accelerated pathological evaluation, providing efficient and precise support for clinical decision-making. Future work may focus on enhancing model robustness through integration with advanced algorithms and validating performance across multicenter clinical datasets. The model also holds promise for deployment in digital pathology platforms and artificial intelligence-assisted diagnostic workflows, improving screening efficiency and promoting consistency in pathological classification.

Humans↗

Changes in cancer registry coding for lymphoma subtypes: reliability over time and relevance for surveillance and study.

Because lymphoma comprises numerous histologic subtypes, understanding the reasons for ongoing increases in its incidence requires surveillance and etiologic study of these subtypes. However, this research has been hindered by many coexisting classification schemes. The Revised European American classification of Lymphoid Neoplasms (REAL)/WHO system developed in 1994 and now used in clinical settings was not incorporated into the International Classification of Diseases-Oncology (ICD-O), used by cancer registries, until the release of the third edition (ICD-O-3) in 2001. Studies including patients diagnosed before 2001 may have codes from earlier ICD-O versions that must be converted to ICD-O-3 and have higher proportions of unclassified (e.g., lymphoma and not otherwise specified) cases. To better understand (a) the agreement of computer-converted ICD-O-3 codes to ICD-O-3 codes generated directly from diagnostic pathology reports and (b) the reproducibility of unclassified status, we reviewed a population-based series of diagnostic pathology reports for lymphoma patients diagnosed before (1988-1994; n = 1,493) and after (1998-2000; n = 1,527) the REAL/WHO scheme was introduced. Overall, computer- and coder-assigned ICD-O-3 codes agreed for 77% of patients in both groups and improved slightly (82%) when codes were grouped. The most common lymphoma subtypes, diffuse large B cell and follicular, had relatively good reliability (84-89%) throughout the study period. T-cell and natural killer cell lymphomas had worse agreement than B-cell lymphomas, even when grouped. Many (42-43%) lymphomas reported as unclassifiable could be assigned a subtype upon pathology report review. These findings suggest that the study of lymphoma subtypes could be improved by (a) use of more standardized terminology in pathology reports, (b) grouping individual ICD-O-3 codes to reduce misclassification bias, and (c) routine secondary editing of unclassified lymphomas by central cancer registries.

Adult↗

Relationship between immunoexpression of mucin peptide cores MUC1 and MUC2 and Lauren's histologic subtypes of gastric carcinomas.

Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This histological classification mirrors histogenetic hypotheses according to which the intestinal-type cancer derives from intestinal metaplasia and dysplasia, while the diffuse-type originates directly from gastric mucosa, with or without a preceding non-metaplastic dysplasia. Studies concerning mucins expression in gastric neoplastic and preneoplastic lesions have provided contradictory data concerning such histogenetic relationships. The aim of the present study was to verify whether a correlation between mucins phenotype and Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided, according to Laurèn's classification, into 27 intestinal-type, 10 diffuse-type and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical expression. Intestinal-type carcinomas displayed a MUC1-positive staining in 23/27 cases and a MUC2-positive immunoreaction in 10/27 cases. Diffuse-type carcinomas expressed MUC1 in 3/10 and MUC2 in 8/10 cases, respectively. According to the mucins expression pattern, three phenotypes were identified: the gastric phenotype (MUC1+/MUC2-); the gastro-intestinal phenotype (MUC1+/MUC2+) and the intestinal phenotype (MUC1-/MUC2+). The gastric phenotype was significantly higherin intestinal-type adenocarcinomas, whereas cases showing an intestinal phenotype were significantly more frequent in diffuse-type adenocarcinomas. These findings provide evidence for a lack of correlation between Lauren's classification and MUC1 and MUC2 phenotypes. In particular, the term intestinal-type tumour as referred to gland-forming gastric cancer does not seem to reflect an immunohistochemical phenotype.

Adenocarcinoma↗

Yes-Associated Protein (YAP)1 and β-Catenin Immunohistochemistry as a Surrogate Marker for GTF2I-Mutant Type A/AB Thymomas.

Thymomas are rare thymic epithelial tumors classified by the World Health Organization into type A/AB thymomas, which commonly harbor GTF2I mutations and behave indolently, and type B thymomas and thymic carcinomas, in which these mutations are less common. Type A and AB thymomas are uniquely enriched for a recurrent somatic hotspot mutation in GTF2I p. L424H; yet, this gene is rarely included in clinical sequencing panels, limiting its diagnostic utility. Yes-associated protein (YAP)1, the principal effector of the Hippo signaling pathway, and β-catenin, the central transcriptional effector of the Wnt pathway, have emerging roles in thymoma biology; however, their relationship to GTF2I mutation status and histologic subtype has not been systematically characterized. We analyzed The Cancer Genome Atlas thymoma data set and an institutional cohort of 38 thymic epithelial tumors to evaluate YAP1 and β-catenin immunohistochemistry (IHC) as surrogate markers for GTF2I mutation status and histologic classification. In The Cancer Genome Atlas data set, YAP1 and CTNNB1 mRNA expression were markedly elevated in type A/AB thymomas relative to type B and carcinoma subtypes, and GTF2I-mutant tumors exhibited significantly higher YAP1 mRNA expression than GTF2I-wildtype tumors. Targeted next-generation sequencing of our institutional cohort confirmed enrichment of the canonical GTF2I p. L424H hotspot in indolent subtypes. By IHC, both nuclear YAP1 positivity and cytoplasmic β-catenin localization were significantly more frequent in indolent thymomas. Cytoplasmic β-catenin demonstrated high specificity (94%) for indolent histology, supporting its use in diagnostically challenging cases such as type A versus type B3 distinction on small biopsies. YAP1 IHC showed a high negative predictive value for GTF2I mutations, such that a YAP1-negative result reliably excludes a GTF2I-mutant tumor. These findings implicate crosstalk between Hippo and Wnt signaling in GTF2I-mutant thymomas and position YAP1 and β-catenin IHC as accessible, cost-effective surrogates for molecular subtyping in a tumor where standard sequencing panels have limited coverage.

GTF2I↗

Primary cutaneous lymphomas: a review with current treatment options.

Primary cutaneous T- and B-cell lymphomas are a heterogenous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria have enhanced the recognition of primary cutaneous T- and B-cell lymphomas. Compared to their nodal counterpart they have a different clinical behavior and therefore require a different treatment approach. Independent predictive factors identified clinically, histologically, and by immunopheno- and immunogenotyping are essential to assess the appropriate treatment for each subtype. The European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Study Group provide a classification of cutaneous lymphomas taking into account of the histological and molecular features. Based on this classification we will provide a summary of the current medical literature in diagnosis, treatment, and prognosis for primary cutaneous lymphomas with emphasis on new treatment strategies.

Antibodies, Monoclonal↗

[Monoclonal antibody against an urinary protein secreted from the renal tubules--immunohistochemical analysis of renal cell carcinoma].

BACKGROUND: Monoclonal antibodies (mABs) against urinary proteins originated from renal tubules were obtained in order to find a possible tumor marker for renal cell carcinoma. METHODS: Urine samples were collected from healthy adult males. After removal of Thamm-Horsfall protein (THP) by sodium chloride precipitation, supernatant urine was ultrafiltered, thus, THP-free urinary proteins were obtained. Then, proteins of plasma origin were removed by circulating the urinary proteins through an affinity column which contained immobilized rabbit anti-human whole serum immunoglobulins. BALB/c mice were immunized with the THP- and plasma protein-free urinary proteins. The spleen cells were fused with mouse myeloma cells. Hybridomas were screened by indirect immunofluorescence of fresh frozen kidney tissue sections using culture supernatants. RESULTS: Five hybridomas producing mAbs which reacted with renal tubular segments were established. One mAb reacted strongly with distal renal tubules. Using this mAb, formalin fixed and paraffin embedded sections of 39 renal cell carcinomas were stained by immunoperoxidase method. Twenty-six of the 39 cancer tissues (66.7%) were stained positive. According to the histological classification, positive staining rate of clear cell subtype, and mixed subtype was 75% (6/8), 80% (8/10) and 66.7% (6/9), respectively. According to the tumor grade, positive staining rate of G1, G2, G3 was 66.7% (6/9), 71.4% (15/21) and 55.5% (5/9), respectively. CONCLUSION: These findings indicate that most of renal cell carcinomas were originated from common precursor cells for both proximal and distal tubules, because normal proximal tubular cells were not stained by the mAb.

Adult↗

A molecular signature of the Nottingham prognostic index in breast cancer.

The Nottingham prognostic index (NPI) is a widely used clinicopathological staging system for breast cancer prognostication. Using a step-wise classification approach where breast tumor expression profiles were first divided into general "molecular subtypes" [estrogen receptor (ER)+, ER-, ERBB2+], followed by an independent analysis of each subtype, we identified a 62-gene expression signature (NPI-ES) highly correlated to the NPI in ER+ tumors. The NPI-ES classified the majority of ER+ tumors into two distinct groups with high confidence and was significantly correlated to NPI status in two independent sets of ER+ tumors derived from different centers. The NPI-ES is comparable to the classical NPI in identifying patients likely to exhibit a poor clinical prognosis, as well as to a recently described "prognosis signature" for breast cancer. Our findings demonstrate how expression profiling can complement classical staging systems employing histopathological parameters scored over a continuous range of values.

Breast Neoplasms↗