Architectural Grade Research Articles

Interobserver agreement for tumour type, grade of differentiation and stage in endometrial carcinomas.

The histopathologic evaluation plays a major role in subdividing endometrial carcinomas into treatment groups. We have evaluated the interobserver agreement regarding tumour type, grade of differentiation, stage and stage I low and high risk cases. A total of 177 cases of endometrial carcinoma in which a hysterectomy and a bilateral salpingo-oophorectomy were performed, were reviewed by three examiners. A variety of features including tumour type, architectural grade, nuclear grade, FIGO grade, and spread/metastases were recorded, and the FIGO stage was determined. Using two different definitions low and high risk groups in stage I tumours were separated. A kappa value was calculated for each of the various parameters. The current study showed a good strength of agreement for tumour type, myometrial invasion, spread/metastases, and FIGO stage (kappa 0.62-1.00). For two of the examiners good agreement was found as to architectural grade (kappa 0.71) while the kappa value for nuclear grade was lower (0.56). As nuclear grading is included in the revised FIGO recommendation a precise definition of nuclear atypia is needed. In stage I tumours very good agreement was demonstrated as to the defined low and high risk group (Kappa 0.64-0.86).

Ki67 Antigen Immunostaining (MIB 1 Monoclonal Antibody) in Serous Ovarian Tumors: Index of Proliferative Activity with Prognostic Significance

The purpose of this study was to evaluate the biological significance of Ki67 antigen expression in serous ovarian tumors, through the analysis of MIB 1 monoclonal antibody reactivity in cystoadenomas, borderline tumors, and invasive cystoadenocarcinomas; the correlation between this index of cell proliferation and clinicopathologic parameters (FIGO stage and grade, and disease-free survival) was also investigated in invasive cystoadenocarcinomas. Fifty-four patients with serous ovarian tumors, treated at the Institute of Gynecologic and Obstetrics, Ancona University, Italy, were used as study population; 10 women had serous cystoadenoma, 16 women had serous borderline tumor, and 28 women had invasive cystoadenocarcinoma. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Compared to cystoadenomas and borderline tumors, the tissular Ki67 antigen immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 2 and 3 neoplasms ( P < 0.001). Within the cystoadenocarcinomas, a relationship was observed between the measured proliferation index and disease FIGO stage, but it was not significant ( P = 0.92). However, patients who recurred and/or had disease progression presented a primitive neoplasm with significantly higher expression of Ki67 antigen than that of patients with disease-free survival ( P = 0.01). A significant relationship was observed between the Ki67 index and disease-free survival, independent of histologic grade and stage, evaluated by Cox hazards analysis ( P = 0.02). The proliferation index detected by Ki67 antigen immunostaining may represent an indicator of aggressiveness in serous ovarian tumors and an additionally useful prognostic factor in cystoadenocarcinomas, probably independent of and apparently more significant than the tumor architectural grade and the disease FIGO stage.

The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system. A Gynecologic Oncology Group study.

The histologic grade of endometrial adenocarcinoma is related to the aggressiveness of the tumor and probability of death from disease. However, the ideal system for assignment of histologic grade remains controversial. In 1988, the International Federation of Gynecology and Obstetrics (FIGO) revised its recommendations for grading typical endometrial adenocarcinoma, such that grade is determined primarily by the architecture of the tumor and secondarily modified in the presence of "notable nuclear atypia"; this phrase, however, has never been defined, and therefore the prognostic validity of this system is unknown. Seven hundred and fifteen women with clinical Stage I and occult Stage II endometrial adenocarcinomas (excluding serous or clear cell type) entered on a Gynecologic Oncology Group protocol, and those treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective pelvic and para-aortic lymph node sampling formed the study population. All cases were centrally reviewed and assigned an architectural grade and a nuclear grade using specific criteria. The FIGO grade was then determined. The various grading methods were examined based on ability to stratify patients into groups with differing rates of disease progression and relative survival at five years. The architectural grade, nuclear grade, and FIGO grade of tumors each were used to separate patients into groups with statistically significant different rates of progression of disease and relative survival. The FIGO modification of architectural grade resulted in the reassignment of 44 patients into a higher grade. The outcome for these 44 was worse than for the remaining patients in the initial grade but was similar to the group into which they were moved. If clearly specified criteria for architectural and nuclear grading are used and "notable nuclear atypia" is defined as grade 3 nuclei, the 1988 FIGO grading system has prognostic utility. The authors recommend this system as the standard method for the grading of typical endometrial adenocarcinoma.

P53 protein and c-erbB-2 protein (p185) expression in endometrial adenocarcinoma of endometrioid type. An immunohistochemical examination on paraffin sections.

The expression of both the nuclear protein p53 tumor suppressor gene product and the transmembrane C-erbB-2 protein oncogene product (p185) correlates to risk factors and outcomes in different tumor types. Their value as prognosticators in endometrial adenocarcinoma of endometrioid type (EC) has not been determined. Paraffin sections were examined immunohistochemically to study the expression of p53 protein and p185 in 112 patients with EC. p53 protein was overaccumulated in 34% and p185 in 13% of the tumors. p53 protein correlated with mitotic count and nuclear grade. Both p53 protein and p185 correlated significantly with outcome. However, they did not correlate with each other or with architectural grade or stage (which defines a high risk group), indicating a role as adjuvant prognosticators in EC. Stage and outcome did correlate, however. Both p53 protein and p185 antibodies work well on routine, formalin-fixed, paraffin-embedded tissue and are easily used in routine diagnostic procedures.

Expression of MIB-1 (Paraffin ki-67) and AgNOR Morphology in Endometrial Adenocarcinomas of Endometrioid Type

Cell kinetic information is an important adjuvant to histologic grading and to stage in some malignant tumors. Some studies have shown that in endometrial carcinomas, flow cytometric S-phase correlates with known prognostic parameters. In the current study, the expression of silver-stained nucleolar organizer regions (AgNORs) and MIB-1 (ki-67-paraffin) was assessed on paraffin sections in 112 endometrial adenocarcinomas of endometrioid type (EC) (49 hormone users, 63 nonusers). The AgNOR morphology correlated significantly with MIB-1, mitotic count, and nuclear and architectural grade, but not with stage or previous hormone treatment. MIB-1 correlated with all the above parameters except myometrial invasion and stage. Only myometrial invasion and stage correlated with short-term outcome; in such cases tumors from hormone users and nonusers were pooled. The median MIB-1 value was significantly lower in EC from hormone users compared with EC from nonusers; moreover, when tumors from hormone users and nonusers with poor outcome were examined separately, only 29% (four of 14) of the tumors expressed MIB-1 less than the medians in the respective groups, indicating that a prognostic cutoff point may be different in the two groups. Because hormone replacement therapy is very common, this observation has implication for future studies of growth fraction in EC. This is the first study to show that AgNOR morphology is significantly correlated with other markers of growth fraction and histologic grade.

Proliferating cell nuclear antigen in endometrial adenocarcinomas of endometrioid type correlated with histologic grade, stage, previous hormonal treatment, and survival

Only a small number of endometrial carcinomas have been examined for proliferating cell nuclear antigen. The results indicate that a high proliferating cell nuclear antigen content correlates with a poor prognosis. One hundred eight endometrial carcinomas of endometrioid type were examined with the monoclonal antibody PC10 (48 tumors from postmenopausal estrogen users and 60 tumors from nonusers). The PC10 content was weakly but significantly correlated with mitotic count and architectural grade, but not with nuclear grade, stage, or survival. PC10 values in estrogen users were much lower (median, 14%) than in nonusers (median, 26%); the difference was independent of histologic grade and stage. After a median follow-up of 30 months (range, 12 to 66 months) 17 patients had died. The cause of death was established as cancer in only nine cases. No overall difference in PC10 values existed between survivors and nonsurvivors. However, if only the estrogen nonusers were examined the survivors showed a mean PC10 value of 27%, while the nonsurvivors showed a mean PC10 value of 45%. The present study indicates that carcinomas from patients with and without previous hormonal treatment are different with regard to their PC10 content. The quantitative and qualitative estimates of PC10 correlated well.

Endometrial Adenocarcinoma Involving Adenomyosis without True Myometrial Invasion Is Characterized by Frequent Preceding Estrogen Therapy, Low Histologic Grades, and Excellent Prognosis

We reviewed cases of endometrial adenocarcinoma to characterize the carcinomas that involved foci of adenomyosis in contrast to the carcinomas that invaded into the myometrium. We encountered 18 cases in which tumor involved foci of adenomyosis without myometrial invasion. There were no cancer-related deaths in these 18 cases over a minimum follow-up period of 5 years. Myometrial invasive tumor was present in 43 cases. Eight of these 43 patients died within 5 years. History of postmenopausal use of estrogen of longer than 6 months duration was obtained in 9 of the 18 patients (50%) with carcinoma confined to adenomyosis compared with 8 of the 43 (19%) with myometrial invasive carcinoma. Only 1 of the 18 cases with adenocarcinoma involving adenomyosis had architectural or nuclear grade III carcinoma compared to 12 of the 43 patients with myometrial invasive carcinoma. Adenocarcinomas involving adenomyosis were characterized by frequent preceding estrogen use, low histologic grades, and excellent prognosis.

International federation of gynecology and obstetrics staging of endometrial cancer 1988

In 1988, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexa, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were (1) the use of the depth of myometrial invasion and (2) the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes. Preoperative endocervical curettage was no longer necessary. Currently, the high level of operability of patients with endometrial carcinoma makes this staging system a viable one, which will provide information about the need for additional treatment. The use of the grading system for the tumor also was refined to upgrade nuclear changes that were inappropriate for the architectural grade. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading took precedence. Adenocarcinomas with squamous differentiation were graded according to the nuclear grade of the glandular component.

Stereological estimate of nuclear volume in endometrial adenocarcinoma of endometrioid type: reproducibility and intra-tumour variation.

Stereological volume weighted mean nuclear volume estimate (Vv) is reported to be highly reproducible and to provide excellent prognostic information for some tumours. The aim of the present study was to investigate the reproducibility and the intra-tumour variation of nuclear Vv and compare it with a morphometric nuclear estimate, i.e. the mean shortest nuclear axis, and with conventional histopathological parameters used in the grading of endometrial adenocarcinomas. Sixty-three endometrioid adenocarcinomas were included in the study. Both Vv and mean shortest nuclear axis showed an acceptable reproducibility and the correlation between them was moderate (Spearman test; rs = 0.8). One-third of the tumours showed a marked intra-tumour variation. A considerable discrepancy between Vv and/or mean shortest nuclear axis and nuclear and architectural grade was found.

Identification of patients with stage I uterine endometrioid adenocarcinoma at high risk of recurrence by DNA ploidy, myometrial invasion, and vascular invasion

The presence of vascular invasion-associated changes (VIAC), which include vascular invasion by tumor and/or the presence of myometrial perivascular lymphocytic infiltrates, has been previously described as a key prognostic indicator in patients with stage I endometrioid (typical) adenocarcinoma of the uterus. In the current report, the prognostic significance of DNA ploidy in addition to other clinical and pathologic features including VIAC was determined in 57 previously examined stage I endometrioid adenocarcinomas of the uterine corpus. By univariate analysis, age at the time of diagnosis, architectural and nuclear tumor grades, DNA ploidy, depth of myometrial invasion, and the presence of VIAC all correlated with clinical outcome. By multivariate survival analysis, only the depth of myometrial invasion, DNA ploidy, and VIAC were found to significantly correlate with survival. A statistical model based on these three features permits stratification of patients into four risk groups with 93, 67, 38, and 10% survival, respectively.

Combined assessment of vascular and myometrial invasion as a model to predict prognosis in stage I endometrioid adenocarcinoma of the uterine corpus.

The prognostic significance of vascular invasion as compared with other pathologic features was evaluated in 102 cases of endometrioid adenocarcinoma confined to the uterus (Stage I) treated by hysterectomy. By univariate analysis, survival most closely correlated with patient age, architectural grade, depth of myometrial invasion, vascular invasion, and the presence of perivascular lymphocytic infiltrates. Among these, vascular invasion and the presence of perivascular lymphocytic infiltrates were the best indicators of prognosis. In contrast to perivascular lymphocytic infiltrates, the presence of a lymphocytic infiltrate at the tumor-myometrial junction was not related to outcome. The presence of vascular invasion was found to be associated closely with perivascular lymphocytic infiltrates. These two features may be related biologically and were designated "vascular invasion-associated changes." By multivariate analysis with the Cox proportional hazards model, the depth of myometrial invasion and the presence of vascular invasion-associated changes were found to provide a highly reliable model for predicting outcome. The highly predictive value of vascular invasion as a prognostic factor in Stage I endometrial carcinoma suggests that it is the mechanism by which occult metastasis develops in patients whose disease progresses after hysterectomy. It is likely that other variables correlating with recurrence, such as the presence of deep myometrial invasion and high tumor grade, may act by increasing the probability of vascular invasion and subsequent metastasis.

The significance of squamous differentiation in endometrial carcinoma. Data from a gynecologic oncology group study

Squamous differentiation is identified in about 25% of endometrial adenocarcinomas (AC). Its significance has been the subject of debate for decades, and it has been reported that the prognosis of adenoacanthoma (AA) is better than, the same as, and worse than that of AC. Part of this confusion has resulted from semantic differences relating to the use of AA and adenosquamous carcinoma (AS). To investigate the prognostic importance of squamous differentiation in endometrial carcinomas and compare the prognostic utility of two classification systems, 456 women were studied who had typical AC and 175 women who had typical AC containing areas of squamous differentiation (AC + SQ) and who had been entered in a Gynecologic Oncology Group protocol of Stage I and II endometrial adenocarcinoma. Assessment of histologic grade and depth of invasion was done both by the pathologist at the member institution and at a second highly structured review. Differentiation of the squamous component of endometrial carcinomas was found to parallel that of the glandular component in most tumors. The biologic behavior of endometrial carcinomas with squamous elements was similar, but not identical, to that of typical AC. Although the frequency of nodal metastasis was similar for both AC and AC + SQ, the presence of squamous elements was associated with an increased probability of survival. Division of AC + SQ by depth of myometrial invasion and by architectural grade of the glandular component provided useful prognostic information that was superior to that resulting simply from division of AC + SQ into AA or AS. The authors recommend that these terms be replaced by "adenocarcinoma with squamous differentiation" and that the pathologist provide information on the architectural grade and depth of myometrial invasion to guide the gynecologist in determining appropriate therapy.

Evaluation of the reproducibility of the revised 1988 international federation of gynecology and obstetrics grading system of endometrial cancers with special emphasis on nuclear grading

An intraobserver and interobserver analysis of the reproducibility of the revised 1988 International Federation of Gynecology and Obstetrics (FIGO) grading system of endometrial cancers was performed in 47 endometrial cancers (94 biopsy specimens). In the revised FIGO grading system the growth pattern still serves as the basic parameter, but nuclear atypia inappropriate for the architectural grade, raises the grade by 1. Ninety-four slides were graded twice by two pathologists. Analysis by the kappa statistics (corrected for agreement by chance) showed an acceptable result for interobserver reproducibility: kappa value 0.65 (95% confidence interval, 0.480 to 0.818). Further study showed this to be a reflection of the reproducibility of the architectural grade: kappa 0.70 (95% confidence interval, 0.565 to 0.850), whereas the reproducibility of the nuclear grade was poor: kappa value 0.55 (95% confidence interval, 0.383 to 0.713). Review of the literature showed great variability in the definition of nuclear grading, indicating that the revised 1988 FIGO grading system is not applicable as standard of reference for studies of endometrial cancers, before agreeing to the definition of inappropriate nuclear atypia.

In vitro sensitivity of human endometrial cancer to cytotoxic and biologic agents.

A goal of cancer research continues to be a better understanding of tumor cell growth and possible ways to modify it. If we learn from preclinical studies which factors are able to modify cell growth, there are oftentimes therapeutic decisions that can be made that ultimately improve patient care. In a clinical setting, the simplest observation to be made is the geographic extent of tumor growth, an assessment made when a patient first presents with a malignancy. Extent of disease determinations have been standardized as tumor stage [1]. Sophisticated imaging techniques and even surgical exploration have been applied as a means to detect clinically inapparent tumor extension. In the example of endometrial cancer, more detailed predictive information following surgery can be obtained by microscopic studies of tumor invasion into the myometrium, the architectural grade (FIGO) and the nuclear grade of the tumor [2, 3]. Predictions of recurrence probabilities can be made, based upon these morphologic and/or geographic parameters. The proliferative activity of a tumor, as determined by flow cytometry, is also significantly related to prognosis [4]. Other biologic parameters that relate to growth of endometrial cancers have been identified, such as the presence or absence of steroid hormone receptors on tumor cells. Receptors can predict tumor growth in response to certain types of treatment [5].

False-negative peritoneal cytology in metastatic ovarian carcinoma

Seventy-nine laparotomies for disseminated intraperitoneal ovarian carcinoma were reviewed to determine the frequency and possible causes of false-negative peritoneal cytology. Negative peritoneal cytology (defined as any reading other than positive) was found in 16 of 79 cases (20%). False-negative cytology occurred more frequently with peritoneal washings (48%) than with ascites (6%; P less than .001); with second-look surgery (50%) than at primary surgery (12%; P = .004); with peritoneal metastasis less than 0.5 cm (50%) than with metastasis greater than 0.5 cm (16%; P = .02); and with bloody cytology specimens (25%) rather than specimens without blood (0%; P = .06). Volume of peritoneal specimen, architectural grade, cytologic grade, and stage of disease (III versus IV), did not affect the frequency of false-negative cytology. The high prevalence of negative cytology associated with peritoneal washings, small tumor size, and second-look surgery suggests that negative cytology is a result of poor distribution of peritoneal washings and infrequent exfoliation of malignant cells rather than misinterpretation of malignant cells present in cytology specimens.

Atmospheric Corrosion of Anodised Aluminium exposed over a Twelve Year Period in the Main Centres of New Zealand

A study of the effect of atmospheric corrosion on an architectural grade of aluminium had been made in Christchurch, New Zealand. This initial work was then extended to cover the main centres of the country. A range of test coupons including the as received ‘mill finish’ condition and the identical material protected with three different thicknesses of anodic coatings were exposed at main centre sites plus a rural site for comparison purposes. The initial aim was to produce visual indications of behaviour in the atmosphere and this was later expanded to include weight loss data. After the preparation of the data obtained in a range of Christchurch atmospheres, a twelve year period for the wider range of sites has now elapsed and these results are now reported. The same range of test coupons has also been exposed in an accelerated corrosion rig and the results from this are included for comparison purposes.

Atmospheric Corrosion of Anodised Aluminium Exposed over a Twelve Year Period in New Zealand

AbstractA study of the effect of atmospheric corrosion on an architectural grade of aluminium alloy was made in Christchurch, New Zealand. A range of test coupons including the ‘mill finish’ condition and identical material protected with three different thicknesses of anodic coatings has been exposed at five sites for comparison purposes. Initially the object was to produce a set of coupons that could be used to give a visual indication of the behaviour of the test coupons in a variety of local atmospheres. After exposure for twelve years, weight change data have now been processed. During this period the same range of coupons has been exposed in an accelerated corrosion rig and the results are also included for comparison.