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PubMed2004

Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities.

Nasal NK/T cell lymphoma is a distinctive type of extranodal lymphoma with an unique immunophenotype and a strong association with Epstein-Barr virus (EBV). It is one of the common extranodal lymphomas in Taiwan. We studied 22 cases of nasal NK/T cell lymphoma to characterize their clinicopathologic features and to explore the possible differences between histologic subtypes and their clinical behavior as well as the prevalence of 30-base pair (bp) deleted latent membrane protein-1 (LMP-1) gene of the EBV. They consisted of 5 cases of small cell type (SC), 6 cases of medium-sized cell type (MC), 6 cases of large cell type (LC), and 5 cases of pleomorphic cell type (PC). Twelve patients were men and 10 were women (1.2 to 1), and their ages ranged from 34 to 75 years with a median age of 55.5 years. The median ages of the LC type and PC type were older than the other 2 types. No other clinical features differed significantly among the 4 subtypes. Nasal obstruction was the most common initial presenting symptom. All but 1 case had stage IE disease at the time of diagnosis. Five cases developed extranasal involvement and skin was the most common site. No bone marrow involvement was detected. The majority of patients received local radiotherapy and chemotherapy. Local irradiation was more effective than chemotherapy alone. We achieved an overall survival of 63.6% at 5 years as estimated by the Kaplan-Meier analysis, which was better than other series. All cases displayed an immunophenotypic profile of CD3(epsilon)+, CD20-, CD56+, and TIA-1+ except that 1 case was CD3(epsilon)-. Fourteen of 22 cases (64%) expressed LMP-1. Nine cases of various cell types (41%) were also CD30+. Among the 4 histologic subtypes, the SC type differed from the other types by the absence of angiodestruction and necrosis, although angioinvasive growth was seen in 2 of them. Pseudoepitheliomatous hyperplasia was seen in only 3 cases of the SC type, and all 5 cases of the SC type were CD30-. No statistical difference in survival was found among the 4 histologic subtypes or between CD30+ and CD30- cases. All 22 cases were positive for EBV by polymerase chain reaction and Epstein-Barr virus early RNA (EBER) in-situ hybridization. A high prevalence rate of 86% (19/22) of the 30-base pair (bp) deleted LMP-1 gene was found, but 81.5% (22/27) of the EBV-positive control reactive lymphoid tissues also had the 30-bp deleted LMP-1 gene. Therefore, the high prevalence of the 30-bp deleted LMP-1 gene found in NK/T cell lymphoma could be due to the high prevalence of the deleted variant in this geographic region. However, it remains possible that the high prevalence of the deleted LMP-1 gene contributed to the increased incidence of EBV-associated nasal NK/T cell lymphoma in Taiwan.

Adult↗
PubMed2004

Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue.

OBJECTIVES: To investigate the histologic subtypes of renal cell carcinoma (RCC) with respect to differences in immunoreactivity for p53 and its impact on prognosis. The prognostic significance of p53 in RCC remains to be defined. METHODS: A total of 188 primary RCC and 58 RCC metastasis specimens were stained immunohistochemically for p53 overexpression using a tissue microarray technique. p53 overexpression was analyzed semiquantitatively with respect to its association with pT stage, grade, histologic subtype, and sex using the chi-square test or Fisher's exact test. The impact on metastasis-free survival was analyzed using the Kaplan-Meier method and log-rank test. For conventional RCC, a multivariate analysis, including pT stage, grade, and p53 immunoreactivity was performed. RESULTS: Sufficient tumor tissue was present in 184 (97.9%) of 188 primary and 56 (96.6%) of 58 metastatic cases. p53 overexpression was found in 42 (22.8%) of 184 primary RCC specimens and in 29 (51.8%) of 56 metastasis specimens (P = 0.0001). p53 overexpression for papillary, chromophobe, and conventional RCC was 70.0%, 27.3%, and 11.9%, respectively (P <0.0001). No association of p53 immunoreactivity with the other parameters investigated was found. Regarding prognosis, a statistically significant difference in metastasis-free survival between p53-positive and p53-negative tumors was found only for conventional RCC (P = 0.0005) and not for the other subtypes (P = 0.19). Multivariate analysis proved grade (P <0.0001), pT stage (P = 0.01), and p53 overexpression (P = 0.01) to be independent prognostic factors for conventional RCC. CONCLUSIONS: p53 overexpression was significantly more frequent in "nonconventional" RCC subtypes, especially papillary RCC, compared with conventional RCC in our study. However, p53 immunoreactivity is a prognostic marker only for conventional RCC.

Adult↗
PubMed1984

Dietary vitamin A and lung cancer risk: an analysis by histologic subtypes.

A case-control study was conducted based on 427 white males with lung cancer of the squamous, small cell, and adenocarcinoma histologic subtypes and 1,094 white male controls admitted to Roswell Park Memorial Institute between the years 1957 and 1965. The relation between selected dietary factors and lung cancer risk was examined for each histologic subtype while controlling for past cigarette use. Dietary vitamin A was found to be negatively associated with risk for squamous cell and small cell carcinoma, but not for adenocarcinoma of the lung. No significant association was observed, however, between dietary vitamin C, fats, or fiber and any of the lung cancer subtypes. These results suggest that the apparent protective effect of vitamin A in lung cancer may be histologic type-specific.

Adenocarcinoma↗
PubMed1997

Correlation of histologic subtypes of primary basal cell carcinoma and number of Mohs stages required to achieve a tumor-free plane.

BACKGROUND: Certain histologic subtypes of basal cell carcinoma (BCC) behave more aggressively and require more aggressive treatment. OBJECTIVE: The aim of this study was to see whether certain subtypes of BCC require more Mohs stages to achieve tumor-free margins. METHODS: A retrospective study of 342 primary BCCs treated with Mohs micrographic surgery (MMS) was performed identifying the histologic subtype of BCC present and the number of stages required to clear the tumor. RESULTS: The aggressive subtypes (infiltrative, morpheaform, micronodular, and mixed) were most frequently found when high numbers of Mohs stages were required for cure. CONCLUSION: The more aggressive subtypes of BCC require more MMS stages to achieve tumor-free margins, which is consistent with the concept that these subtypes usually require more aggressive treatment from the start.

Aged↗
PubMed1987

Regional variation in Hodgkin's disease incidence by histologic subtype in the US.

Geographic distribution in Hodgkin's disease (HD) incidence was examined for whites by age, sex and Rye histologic subtype in several regions of the US for 1969 to 1971 and 1973 to 1980, using data from national cancer surveys. Average annual age-adjusted rates (1973-1980) ranged between 2.0 and 3.6 per 100,000 persons. Significant regional variation in HD was confined to elevated rates in Connecticut and San Francisco-Oakland, and low rates in Hawaii, Atlanta, and New Orleans. In young adults (ages 20-34 years) HD was positively associated across regions with rates for children (ages 5-14 years), and with community-wide socioeconomic status (SES), but did not vary with older adult rates. Patterns of geographic variation differed among the histologic subtypes, with no significant variation for the lymphocyte predominance form. Incidence of nodular sclerosis increased with regional SES, and was inversely correlated with rates of lymphocyte predominance. Among women, HD incidence became less heterogeneous across regions with time.

Adolescent↗
PubMed2006

Meningothelioma as the predominant histological subtype of midline skull base and spinal meningioma.

OBJECT: This study was undertaken to test a hypothesis that meningiomas of the midline skull base and spine are predominantly of the meningothelial histological subtype. METHODS: The cases of 794 consecutive patients who underwent resection for meningioma at the Cleveland Clinic between January 1991 and March 2004 were reviewed retrospectively. The authors analyzed the relationship between the tumors' histological subtypes and sites of origin in the 731 patients from this group who harbored tumors that were determined to be benign histologically (World Health Organization Grade I). Meningothelial meningiomas (MMs) accounted for 63.5% (464/731) of the Grade I tumors. The incidence of MM according to the site of origin was as follows: 84.9% (186/219) in the midline skull base, 58.3% (35/60) in the lateral skull base, 48.5% (183/377) in a non-skull base location, and 80% (60/75) in spinal locations. The incidence of MM in the midline skull base and spinal locations were significantly higher than in non-skull base or lateral skull base locations. CONCLUSIONS: Meningiomas of the midline neuraxis are predominantly meningotheliomas. Analysis of the increasingly available data on genetic and topographic characteristics of MMs suggests that they may represent a unique entity, contrary to the prevailing belief that all benign meningiomas are identical tumors.

Humans↗
PubMed1999

Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast.

Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.

Breast Neoplasms↗
PubMedDate not supplied

Discovery of differentially expressed genes related to histological subtype of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world. To identify the histological subtype-specific genes of HCC, we analyzed the gene expression profile of 10 HCC patients by means of cDNA microarray. We proposed a systematic approach for determining the discriminatory genes and revealing the biological phenomena of HCC with cDNA microarray data. First, normalization of cDNA microarray data was performed to reduce or minimize systematic variations. On the basis of the suitably normalized data, we identified specific genes involved in histological subtype of HCC. Two classification methods, Fisher's discriminant analysis (FDA) and support vector machine (SVM), were used to evaluate the reliability of the selected genes and discriminate the histological subtypes of HCC. This study may provide a clue for the needs of different chemotherapy and the reason for heterogeneity of the clinical responses according to histological subtypes.

Algorithms↗
PubMed2001

Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH.

BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy according the International Society of Paediatric Oncology trial & study 9. Standardised preoperative therapy with dactinomycin and vincristine for 4-8 weeks was generally applied in patients between 0.5 and 16 years with localized renal tumors and imaging typical for WT. In 99.5% of cases representative material was sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified Beckwith & Palmer criteria were used. Reduction in volume measured by imaging prior to chemotherapy and surgery was used to assess response (poor response: reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of patients treated with immediate surgery and 12.4% of patients with preoperative therapy in the age group up to 12 months. The difference in age (P = 0.022) was linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58 and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed: stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of epithelial WT) but none relapsed. In the other WT with viable tumor left after preoperative therapy > 70% had good response, poor response was a risk factor (P = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be used in WT after preoperative therapy to stratify postoperative therapy in future. A milder therapy could be tested in differentiated WT at low stages and an intensified in the others with viable tumor left and poor response, i.e., mainly blastemal WT.

Adolescent↗
PubMed2001

Human immunodeficiency virus-related lymphoma: relation between clinical features and histologic subtypes.

PURPOSE: Non-Hodgkin's lymphoma occurs frequently in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We determined the association between the clinical and histologic features of HIV-related lymphoma. SUBJECTS AND METHODS: We reviewed the medical records of 291 patients with noncerebral HIV-related lymphoma who had been treated in multicenter trials coordinated by the Groupe d'Etude des Lymphomes de l'Adulte between 1988 and 1997. This study was performed mainly before the availability of combination antiretroviral therapy. RESULTS: The main histologic subtypes were centroblastic lymphoma in 131 patients (45%), immunoblastic lymphoma in 39 patients (13%), and Burkitt's lymphoma (including the classical form and the variant with plasmacytic differentiation) in 115 patients (40%). Burkitt's lymphoma was the most aggressive form, whereas immunoblastic lymphoma occurred in severely immunodeficient patients. Two-year survival after enrollment was 15% in immunoblastic lymphoma, 32% in Burkitt's lymphoma, and 31% in centroblastic lymphoma (P = 0.006), but multivariate analysis did not confirm the independent prognostic value of histologic subtype. Instead, five independent pretreatment factors increased the risk of mortality: age 40 years or older [relative risk (RR) = 1.5; 95% confidence interval (CI), 1.1 to 2.1; P = 0.005], elevated serum lactate dehydrogenase level (RR = 1.5; 95% CI, 1.1 to 2.1; P = 0.02), having a diagnosis of AIDS before lymphoma (RR = 1.8; 95% CI, 1.2 to 2.6; P = 0.006), CD4(+) cell count less than 100 x 10(6)/L (RR = 1.8; 95% CI, 1.3 to 2.6; P = 0.0004), and impaired performance status (RR = 2.4; 95% CI, 1.7 to 3.4; P <0.0001). CONCLUSION: Several pretreatment characteristics of HIV-related lymphoma were linked to the histologic form, but HIV disease parameters other than those of lymphoma were the main determinants of outcome, so the histologic features of the lymphoma were not associated with prognosis.

Adult↗
PubMed1991

Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma.

Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.

Adolescent↗
PubMed2003

Superficial radiotherapy for patients with basal cell carcinoma: recurrence rates, histologic subtypes, and expression of p53 and Bcl-2.

BACKGROUND: The histologic subtype of a basal cell carcinoma (BCC) may be an important factor for the success of a certain treatment modality. In the current article, the authors report recurrence rates among patients with BCC after superficial radiotherapy as well as Bcl-2 and p53 expression levels stratified by BCC subtype. METHODS: The authors performed a retrospective study of 175 BCCs in 148 patients (64 female patients and 84 male patients; mean age, 69 years) who were treated with radiotherapy. According to their histologic patterns, BCCs were classified as nodular (n = 103), superficial (n = 25), and sclerosing (n = 47). In addition, six patients with metatypic BCC were reviewed. Bcl-2 and p53 protein expression was examined on a tissue microarray of 60 BCC samples (18 nodular tumors, 12 superficial tumors, and 30 sclerosing tumors). RESULTS: The estimated 5-year recurrence rate for all patients with BCC was 15.8%: 8.2% for patients with the nodular subtype, 26.1% for patients with the superficial subtype, and 27.7% for patients with the sclerosing subtype (Kaplan-Meier analysis: P = 0.055). The median follow-up was 48 months. The mean time to recurrence was 20 months, and 86.4% of all recurrences occurred within 3 years after treatment. No gender-specific differences were observed. In addition, one of six metatypic BCCs recurred. Nuclear p53 immunoreactivity and low Bcl-2 expression were significantly correlated with the sclerosing subtype. Overall, 61.5% of patients developed additional neoplasms during follow-up (76 developed additional BCCs, 15 developed squamous cell carcinomas, and 6 developed Bowen disease). CONCLUSIONS: The sclerosing subtype of BCC was a risk factor for recurrence after radiotherapy. In contrast, excellent results were achieved for patients with predominant nodular subtype. Nevertheless, radiotherapy may be the therapy of choice for patients with all BCC subtypes, depending on the individual patient's characteristics. Expression analyses confirmed that p53 and Bcl-2 levels may be used as indicators for the aggressiveness of a BCC subtype. Due to the high incidence of additional skin malignancies, patients with BCC need careful follow-up.

Adult↗
PubMed1996

Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies. PATIENTS AND METHODS: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature. RESULTS: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study. CONCLUSION: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.

Adolescent↗
PubMed2005

Histological subtyping and nuclear grading of renal cell carcinoma and their implications for survival: a retrospective nation-wide study of 629 patients.

OBJECTS: The aim of this study was to evaluate the prognostic significance of the current WHO histological subtyping and Fuhrman nuclear grading on the survival of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective population-based study was carried out on all patients with a histopathologically confirmed diagnosis of RCC in Iceland between 1971 and 2000. Fuhrman grade, TNM stage, and survival were evaluated and multivariate analysis applied in order to determine prognostic factors. RESULTS: Out of 629 patients (387 males, 242 females, mean age 64 years), 558 (88.7%) had clear cell, 53 (8.4%) papillary, and 13 (2.1%) chromophobe RCC. Patient demographics were comparable for the two major subtypes, but chromophobe RCCs were larger in size and were diagnosed at a younger age. Clear cell RCCs were more often of higher grades (G3+G4, 48.4%) and at advanced TNM stages (III+IV, 59.3%) than papillary RCCs (22.6% and 34% respectively, p<0.001). Linear regression analysis showed a strong correlation between grade, tumor size, and stage (p<0.001). Chromophobe RCCs had a better survival in univariate analysis than both papillary and clear cell RCCs (84.6% vs. 66.5% and 54.9% 5-year disease specific survival, p<0.001). However, in the multivariate analysis, only the patient's age, calendar year of diagnosis, TNM stage, and nuclear grade were independent prognostic factors of survival. CONCLUSION: In this complete nation-wide series nuclear grading is important in predicting survival of patients with RCC. It is strongly related to both tumor size and stage, with stage being by far the strongest prognostic factor. Different histological subtypes confer different survival. However, in spite of the distinctive cytogenetic and molecular characteristics of the subtypes, the survival difference is to a large extent due to differences in grade and particularly stage.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Fine needle aspiration cytology of palpable breast lesions. Histologic subtype in false negative cases.

OBJECTIVE: To evaluate the use of fine needle aspiration cytology (FNAC) in the management of benign and malignant breast disease in an outpatient breast clinic and to determine the guidelines for reporting on FNAC of breast lesions, we evaluated the test results in correlation with the histologic diagnosis. STUDY DESIGN: We evaluate the test results of 669 cases of FNAC of the breast in 17 months in our outpatient breast clinic in correlation with the histologic diagnosis, histologic subtype according to the Japan Mammary Cancer Society classification and mammography results in false negative cases. RESULTS: Among 669 cases, 25.3% were inadequate for cytologic diagnosis. An analysis of the results using the two-by-four contingency table, including cases with inadequate cytologic diagnosis, showed that 10.6% and 1.0% had false negative and false positive cytologic diagnoses, respectively; sensitivity and specificity were 76.9% and 91.6%, respectively. The false negative rate of 10.6% was higher than expected, and those belonged mostly to the "inadequate" cytologic diagnosis category even though they were discrete, obviously malignant masses clinically. To try to explain this, we compared the cytologic results and histologic subtype according to the Japan Mammary Cancer Society classification and the mammography results. Of 73 cases of infiltrating ductal carcinoma in which retrospective reexamination of the histology slide was possible, 27 (37.0%) were papillo-tubular type, 11 (15.1%) were solid-tubular type and 35 cases (47.9%) were scirrhous type. Although the scirrhous subtype was only 37.0% in the group in which a cytologic diagnosis of carcinoma was possible, more than two-thirds of the cases of false negative cytology were scirrhous type and had malignant mammographic findings. This finding was statistically significant. CONCLUSION: In cases of ductal carcinoma of scirrhous subtype, the FNAC tended to be inadequate and false negative, but mammography showed better discrimination in such cases.

Biopsy, Needle↗
PubMed1991

Black-white differences in Hodgkin's disease incidence in the United States by age, sex, histology subtype and time.

Black-white differences in Hodgkin's disease (HD) occurrence have been reported in older US mortality statistics and in limited international data, suggesting either genetic or socioeconomic determinants of susceptibility. However, there has been no evaluation with reliable data of the interracial incidence patterns by age, sex, and histologic subtype, that are prerequisite to understanding the causes of such variation. This project utilized 15 years of recent, high quality, incidence data from well-defined black and white US populations to calculate age-, sex-, and histology-specific rates of HD by race over time. Rates were somewhat lower for blacks (N = 593) than whites (N = 8,541) of both sexes, except among young boys. For blacks, age-specific incidence curves were slightly bimodal, although less than for whites; the male excess of HD was larger; and rates among women were low at all ages. For each histology subtype, blacks had lower incidence than whites; however, for the first time, nodular sclerosis was found to be the most common variant for both races. Between 1969-74 and 1980-84, HD rates declined in whites over age 55 but increased in white young adult women; among blacks, rates decreased slightly for boys and young adult men, the latter likely due to improving population enumeration. These findings confirm some interracial differences noted previously in HD. For blacks, they also reveal an incipiently bimodal age incidence and more prominent nodular sclerosis subtype occurrence that support a strong role for environmental factors in racial variation of this lymphoma.

Adolescent↗
PubMed2004

Hyperplastic (serrated) polyps of the colorectum: relationship of CpG island methylator phenotype and K-ras mutation to location and histologic subtype.

We investigated the frequency of promoter region CpG island methylation (CIM) of hMLH1, MGMT, MINT1, MINT2, and p16 and K-ras mutations in a total of 79 hyperplastic (serrated) polyps (HPs) from 75 patients and correlated the molecular profiles to polyp location in the colorectum, histologic variation, and other factors. Methylation-specific PCR (MS-PCR) was used to assay CIM status. HPs that showed CIM of one or more or two or more of the genes assayed were classified as CpG island methylator phenotype (CIMP) and CIMP-high (CIMP-H), respectively. PCR restriction fragment length polymorphism was used to assay K-ras codon 12 and 13 mutations. Logistic regression indicated a statistically significant trend for increasing odds for CIMP (P = 0.002) and CIMP-H (P < 0.001) according to proximity to the cecum or distance from the rectum. Conversely, K-ras codon 12 mutation was present in 13 of 40 (32.5%) distally located HPs compared with 2 of 39 (5.1%) proximal HPs (P = 0.006). Histologic subtype distribution varied by proximal and distal locations. Frequency of CIMP in serrated polyps with abnormal proliferation (SPAPs), differed significantly from goblet cell serrated polyps (GCSPs) (24 of 26, 92.3% vs. 6 of 13, 46.2%) (P = 0.003) and microvesicular serrated polyps (MVSPs) (26 of 38, 68.4%) (P = 0.03). Frequency of K-ras mutation in GCSPs (7 of 13, 54%) differed from that of MVSPs (6 of 38, 16%) (P = 0.01) and SPAPs (2 of 26, 8%) (P = 0.003). Location in the colorectum and histologic subtype were major determinants of the molecular profile of HPs. The molecular findings of CIMP and K-ras mutations appear to encompass most if not all HPs; CIMP profiles suggest that SPAP is the most advanced morphologic variant. We postulate that MVSP and GCSP may be precursor lesions that, if proximally located or larger, can progress to SPAP. Frequent K-ras mutations and infrequent CIMP distinguish the distal GCSP variant.

Adult↗
PubMed2002

Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype.

Both beta-catenin and E-cadherin are epithelial cell adhesion molecules. In addition, beta-catenin is an important element of the Wnt signal transduction pathway, which has been implicated in embryogenesis and carcinogenesis, including the development of endometrial and ovarian endometrioid carcinomas. We hypothesized that the expression pattern of these two adhesion molecules may depend upon the histological subtype of endometrial carcinomas. Therefore, we compared the immunohistochemical expression of beta-catenin and E-cadherin in a set of uterine adenocarcinomas matched for high histologic grade, that is, poorly differentiated (International Federation of Gynecology and Obstetrics [FIGO] Grade III) uterine endometrioid carcinomas and uterine serous carcinomas. Seventeen FIGO Grade III endometrioid adenocarcinomas and 17 serous carcinomas were evaluated histologically and immunohistochemically with commercially available monoclonal antibodies against beta-catenin and E-cadherin. Nuclear expression of beta-catenin was observed in 8 of 17 (47%) endometrioid adenocarcinomas but in none of the serous carcinomas (P = .003). Moderate or strong E-cadherin expression was identified in 7 of 17 (41%) serous carcinomas as opposed to in only 1 of 17 (6%) endometrioid adenocarcinomas (P = .02). The majority of endometrioid adenocarcinomas showed strong beta-catenin expression coupled with weak E-cadherin expression; serous carcinomas did not exhibit a comparable trend. Our results indicate that the expression of beta-catenin and E-cadherin in high-grade endometrial cancers is strongly associated with histological subtype. These data provide further support for the distinct molecular profiles of endometrioid adenocarcinoma and serous carcinoma. Notably, differences in cell adhesion molecule expression could account for variations in patterns of tumor dissemination. The immunohistochemical staining pattern may also be useful for diagnostic purposes.

Cadherins↗