Malignancy Grading System Research Articles

Histological grading in the deep invasive front of T1 and T2 glottic squamous cell carcinomas has high prognostic value.

The characteristics of the deep invasive front area of squamous cell carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, the authors have recently developed a simple malignancy grading system based solely on the characteristics of the deep invasive front area of oral squamous cell carcinomas, which has great prognostic value. Our previous materials were somewhat heterogeneous, and the prognostic value of our system needed to be confirmed in homogeneous patient material. In the present study of 95 T1-2/N0 glottic carcinomas all treated by radiation, the high prognostic value for invasive front grading of biopsy specimens is confirmed. The grading significantly predicted local recurrence, i.e. treatment failure (P = 0.001). Histological characteristics of the deep invasive front proved to be a better indicator of prognosis than the T-category (size of tumour), and our findings may be of value in the selection of treatment. Of the individual variables in the grading system (pattern of invasion, degree of keratinization, nuclear polymorphism and host response), pattern of invasion and degree of keratinization were the strongest prognosticators in the multivariate analyses. Invasive front characteristics may also prove to be of prognostic value in other cancers.

Vimentin in oral squamous cell carcinoma.

The relationship between the histological grading of malignancy and the expression of vimentin and cytokeratin was studied in 43 cases of oral squamous cell carcinoma. Immunohistochemical analysis was carried out with the avidin-biotin method using monoclonal antibody anti-vimentin, and the peroxidase anti-peroxidase method using the polyclonal antibody anti-cytokeratin. All cases were classified according to the histological malignancy grading system proposed by Anneroth. All of the carcinomas were found to express cytokeratin, while 60.4% expressed vimentin. Vimentin was particularly noted in all tumors scored to have highly malignant cells.

T3N0 glottic carcinoma: DNA S-phase as a predictor of the outcome after radiotherapy.

In consecutive series of 326 laryngeal cancer patients, of 29 (9%) with stage T3N0 glottic carcinomas, 23 achieved complete local remission after curative radiotherapy and form the basis of the present investigation. Flow cytometry determinations of DNA-ploidy status and the S-phase fraction, and a "histopathological malignancy grading system" were evaluated as possible patient- and/or tumor-related predictors of local recurrence. Twelve patients (52%) were continuously disease-free after radiotherapy, whereas 10 (43%) manifested local recurrence, and one distant metastasis. The radiotherapy delivered to patients who later suffered from a local recurrence did not differ from those being continuously disease-free. The frequency of local recurrence was significantly correlated to patients whose primary tumours manifested a low S-phase fraction (p < 0.05). A low S-phase fraction may indicate slowly proliferating tumour-cells, which become more radioresistant on exposure to a series of fractionated doses, as their reassortment into sensitive phases will be proportionately slower.

Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients

Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility.

DNA patterns and aggressive histopathologic features in 159 patients with cervical carcinoma.

In 159 patients with invasive squamous cell carcinoma of the uterine cervix, flow cytometric DNA patterns were related to eight histopathologic parameters according to a malignancy grading system, in which four of the parameters concern the tumor cell population and four concern the tumor-host relation. Each parameter was graded from 1 to 3 points. Flow cytometrically aneuploid values, contrasted to peridiploid ones, were more often found in specimens with immature, irregular nuclei, as well as in specimens with diffuse growth (p less than 0.05), obvious vascular invasion (p less than 0.05) or slight or no plasmolymphocytic response (p less than 0.05). For each histopathologic parameter, higher mean S-phase rates were found for the aggressive 3-point tumors than for the 1-point tumors. Tumors with total scores of 11-17 points were more often peridiploid than tumors with 18-22 points.

Prognostic value of a malignancy grading system in treatment of recurrent cervical carcinoma

A malignancy grading system (MGS) comprising 8 histopathological parameters has been used to evaluate the response rate and prognosis for patients receiving chemotherapy for recurrent cervical carcinoma. Seventy-two women were treated with an adriamycin-cyclophosamide-vincristine (ACO) regimen or bleomycin-adriamycin-cisplatin (BAD) regimen. The mean value in the MGS was 16.7 for the primary tumors and 17.4 for the recurrences. Correlations between the individual parameters of the MGS when used on the primary tumors and on the recurrences were low. Only parameters 7 (vascular invasion) and 8 (lymphocytic response) were significantly higher in the recurrences. Responders had significantly longer survival than non-responders (P < 0.001), but the two groups did not differ regarding the malignancy scores for the 8 individual parameters nor for the MGS sums. There was no correlation between the malignancy scores and survival in this selected series of recurrent cervical carcinomas.

Invasive squamous cell carcinoma of the uterine cervix. IX. Construction of a partial index in a histopathologic malignancy grading system.

A malignancy grading system (MGS) for invasive squamous cell carcinoma of the uterine cervix, consisting of four items for the tumour-cell population and four items for the tumour-host relationship, proved to have a good prognostic capacity. A correlation analysis based on 161 patients with invasive squamous cell carcinoma of the uterine cervix in stages I and II was evaluated. The relationships between survival/lethality ratio (S/L) and all single items, MGS, and a reduced partial index were compared. The study showed good agreement with previous studies on another partial index. The MGS had the best predictive value. The items of the tumour-cell population had no significant predictive value. According to a regression analysis, items for the tumour-host relationship or the items vascular invasion and host-cellular response alone could be used without any substantial loss of predictive capacity compared with the MGS. However, the MGS remains the most complete and adequate classification for invasive squamous cell carcinoma of the uterine cervix.

Invasive squamous cell carcinoma of the uterine cervix. VIII. Survival and malignancy grading in patients treated by irradiation in Lund 1969-1970.

The correlation between certain prognostic factors and the 10-year survival/lethality rate was analysed in 168 patients with invasive squamous cell carcinoma of the uterine cervix stage I A-II B treated by radiation therapy from 1969 through 1970. These factors included a malignancy grading system (MGS) consisting of 8 items: structure (P1), differentiation into cell type (P2), nuclear polymorphism (P3), mitosis (P4), mode of invasion (P5), stage of invasion (P6), vascular invasion (P7), and host-cellular response (P8). Histologic differentiation (1) and differentiation into cell type (11), the patient's age, the year of admission, the clinical stage (FIGO), and irradiation were also analysed. Many of these factors were correlated to the prognosis. However, the MGS system was superior as a predictive factor. Patients with a low MGS score had an extremely good survival rate at both the 5- and 10-year controls. The patients with a high MGS score had approximately 55 per cent lethality at 10 years. The MGS was significantly superior to each separate item as well as to each predictive factor (p less than 0.05). Further, no other important predictive factor could be identified after the MGS had been included in the multivariate analyses.

Invasive squamous cell carcinoma of the uterine cervix. V. Late local recurrences after radiation therapy.

In 26 patients with late local recurrent invasive squamous cell carcinoma of the uterine cervix, primary and recurrence biopsies have been compared with respect to a malignancy grading system. In patients with 16 points or more (n = 13) there was no significant change between estimations. In patients scoring less then 16 points (n = 13), 7 patients had a significant rise in tumour host score indicating the possibility of new prognostic factors occurring. The concept of recurrence is discussed against the background of these findings.

Invasive squamous cell carcinoma of the uterine cervix. III. A malignancy grading system for indication of prognosis after radiation therapy.

The predictive value of a malignancy grading system embodied by 8 histopathologic parameters and of staging, age, year of admission and the different treatment modalities were compared in relation to 5- and 8-year survival. The material consisted of 196 patients in stage II according to the FIGO classification. The grading system proved superior with high significance (p less than 0.001) to the other predictors including each histopathologic parameter apart from vascular invasion (p = 0.01). All histopathologic parameters but 2 (differentiation into cell type and mitosis) exhibited significant (p less than 0.01) decrease in survival with higher grade at the 5- and 8-year controls. Patients in stage II could be divided into groups with low, intermediate and high malignancy points. Both groups of extremes showed a marked and highly significant difference in survival rates compared with the intermediate group, and the grading system made it possible to predict 60 per cent of the patients with acceptable specificity. In the group of high malignant tumours the system maintained a continual prognostic value even among patients still alive at the 5-year control.

Invasive squamous cell carcinoma of the uterine cervix. II. Reproducibility of a histopathologic malignancy grading system.

A histopathologic malignancy grading system for invasive squamous carcinoma of the uterine cervix has previously been presented. The grading results in a total malignancy point value for every patient (range 8-24). This score has been proven to have a significant prognostic value for the individual patient. The inter-observer reproducibility of this system has been examined by two pathologists, on the pretreatment biopsies of 100 patients and the intra-observer reproducibility on 190 patients (observer one) and on 100 patients (observer two). These biopsies were estimated twice and three times, respectively, without knowledge of former results and at an interval of 2 to 6 months. The inter-observer correlation coefficient was 0.54, the intra-observer correlation coefficients 0.94 and 0.74, respectively.

Invasive squamous cell carcinoma of the uterine cervix. IV. Analysis of a histopathologic malignancy grading system and construction of a partial index.

A new histopathologic malignancy index has previously proved capable of permitting discrimination of patients with carcinoma of the uterine cervix (stage II) with respect to prognosis. Eight histopathologic items graded from 1 to 3 add up to constitute the malignancy index. By regression analysis the number of items could be reduced to 4. Seemingly without loss in the prediction value a partial index was elaborated by the following 4 items: mitosis, mode of invasion, cellular response, and vascular invasion, the latter attributed double the weight. The predictive value of the partial index seemed to be as good as that of the previous malignancy index on an independent materials as well.

Invasive squamous cell carcinoma of the uterine cervix. I. Definition of parameters in a histopathologic malignancy grading system.

A histologic malignancy grading system for invasive squamous cell carcinoma of the uterine cervix is presented. The method is based upon evaluation of the tumour cell population in terms cell differentiation, structure, nuclear polymorphism and the frequency of mitotic figures in terms of a 1 to 3 point scale. The tumour-host relationship was also estimated in terms of a 1 to 3 point scale, by the mode of invasion, stage of invasion, vascular invasion and degree of lymphoplasmocytic infiltration. These parameters permitted a grading with 8 to 24 points totally.

Histologic Malignancy Grading of the Primary Tumour as a Prognostic Factor in Breast Cancer

The prognostic value of the histologic malignancy grading system of Eker et al. (1) has been analysed in a prospective clinical study of 864 female breast cancer patients undergoing radical mastectomy. The percentage of patients with tumour infiltration of the axillary nodes was found to increase with increasing malignancy grade of the primary tumour (9% in grade I, 80% in grade IV). When the axillary nodes were not infiltrated, the recurrence rate was low, regardless of the malignancy grade. When the axillary nodes were infiltrated, the recurrence rate increased with increasing malignancy grade, from 34% in grades I and II up to 67% in grade IV. If the infiltration of the axillary nodes had not been known, the histologic grading of the primary tumour alone would have divided the case material into four prognostic groups with a recurrence rate increasing from 12.5% to 53.3%. In those cases where recurrences developed, however, the speed of progression of the disease did not seem to be related to the malig...