Faculty of Medicine

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End date: 1999Subject: search.filters.subject.recurrence

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    Predictive value of estrogen receptors evaluated by immunocytochemical analysis in breast cancer patients
    (Gustav Fischer, 1997-09)
    Yashar, Genghis
    ;
    Ivkovski, Ljube
    ;
    ;
    Zografski, George
    BACKGROUND: The determination of estrogen receptor (ER)status is valuable in selecting the appropriate therapy and predicting prognosis for patients with invasive breast carcinoma. OBJECTIVE: The aim of our study was to assess the predictive value of ER status evaluated preoperatively by immunocytochemical analysis and compared with recurrence rate, clinical and histopathological features in 52 patients with breast carcinoma. MATERIALS AND METHODS: Fifty-two aspirates obtained by fine-needle-aspiration biopsy (FNAB) were prepared as cytospin samples for ER-immunocytochemical analysis (ER-1CA). Cytospin slides were stained using a standard procedure with horseradish peroxidase-antiperoxidase (PAP) method, utilising monoclonal antibody to ER (H222SP, ER-ICA kit, Abbott Laboratories, USA). The assessment of staining was scored in a semiquantitative fashion incorporating the intensity and the distribution of stained cells and the values were designated as IS-CYTOSCORE. All the patients underwent radical mastectomy with axillar lymphadenectomy during the period from September 1990 to March 1992 and were staged according to the postoperative pTNM classification of UICC (1987) guidelines. During the follow-up period (range, 2-75 months, mean 32) recurrences were observed in 25 (48%) patients.ER status was correlated to recurrence rate, age of the patients, type of the breast carcinoma, tumor size, grade of histologic differentiation, desmoplastic reaction, elastosis, necrosis and calcifications. The comparison was made by cross-classification and statistical significance determined by χ2 and Fisher's exact test. RESULTS: ER status was positively detected in 28 (53.8%) patients. There is significant association between ER status and age of the patients (p = 0.02), the type of the breast carcinoma (p = 0.018), and the recurrence rate (p = 0.012). Eighteen out of 26 (70%) patients 50 years or older, were positively related to ER status. In 22 (42.3%) lobular carcinomas, ER status was positive in 16 (73%) patients, compared with 30 (57.7%) ductal carcinomas, with ER status positive for 12 (40%) patients, only. Recurrences were observed in 16 (64%) patients with ER- breast carcinomas and 9 (36%) patients with ER+ breast carcinomas. Less important histopathological features as elastosis and calcifications, demonstrated statistically significant positive relation with ER status (p = 0.004 and p = 0.005, respectively). No significant association was found between the ER status and other histopathological characteristics. CONCLUSION: Our results suggest that recurrences, age of the patients and the lobular type of breast carcinoma are positively correlated with ER status. These data are consistent with the results of other similar studies. On the other hand, the stage of the disease as well as the grade of histologic differentiation and lymph node involvement, demonstrated no significant association with ER status as expected. A small number of cases studied and the heterogeneous stages included, could explain some of the differences between our data and the results from other studies. Semiquantitative ER-1CA, as fast and simple method, is especially useful in determination of ER status in recurrent, metastatic and small-sized breast carcinomas. The great advantage of ER-ICA is in a possibility of ER status preoperative determination, and repeating the procedure, if necessary. Despite the good performances, some inherent difficulties must be noted: subjectivity in scoring and detection by antigenicity of ER. Therefore, ER status quantitative assessment by using Cell-Analysing-System (CAS) and concomitant quantitative measurements of progesterone receptor status, should be of additional benefit.
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    Human papilloma virus DNA presence in early stage cervical carcinomas: Correlation with other prognostic factors and recurrence rate
    (Gustav Fischer, 1997-09)
    ;
    Ivkovski, Ljube
    ;
    Yashar, Genghis
    ;
    Stavrik, George
    BACKGROUND: Although the role of human papillomavirus (HPV) in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. OBJECTIVE: The objective of our study was to assess the prognostic significance of the presence of HPV DNA by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 92 patients with cervical carcinoma..In this report the preliminary results of a larger programme aimed to search for the prognostic factors in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy, followed by postoperative adjuvant pelvic radiotherapy, are presented MATERIALS AND METHODS: Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51 (Enzo Diagnostics, New York). Clinical data and histopathologic features of these patients were analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 48 (52.2%) patients, while local extension to vagina and parametrial tissues was found in 10 (10.9%) and 34 (36.9%) patients, respectively. Pelvic lymph node involvement was found in 25 (27.2%) patients. During the follow-up period (range, 2-87, mean, 35 months), recurrences were observed in 13 patients. Variables were compared by cross-classification and statistical significance was determined by χ2 and Fisher`s exact test. RESULTS: HPV DNA was detected in 41 (44.6%) cervical carcinoma specimens. The prevalence rate of different HPV types was 37% (34) for HPV 16/18, 6.5% (6) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate was significantly higher in patients with HPV DNA negative cervical carcinomas (P=0.02). Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 4.9% (2 cases), compared to 21.6% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, number of positive lymph nodes, histologic subtype, maximum depth of cervical stromal invasion, maximal tumor diameter, longitudinal endocervical involvement, proportionate longitudinal endocervical involvement, tumor-cervix area quotient, maximal and minimal sagittal tumor area, parametrial involvement, vaginal involvement, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, surgical margins involvement, age) were also correlated with the presence of HPV DNA. No statistically significant association was found between the presence of HPV DNA and 17 other clinical and histopathologic variables. On the other hand recurrence rates were significantly related to tumor extent (P=0.0001), presence of regional lymph nodal metastases (P=0.0002), maximal tumor diameter (P=0.14), proportionate longitudinal endocervical involvement (P=0.007), maximal sagittal tumor area (P=0.038), parametrial involvement (P=0.0001), vaginal involvement (P=0.03), and lymph-vascular space invasion (P=0.0023). CONCLUSIONS: The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be related to recurrence rate and unrelated to various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.
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    Prognostic significance of the human papillomavirus DNA presence in early stage cervical carcinoma
    (1996-05)
    ;
    Stavrik, George
    Although the role of human papillomavirus in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. The objective of our study was to assess the prognostic significance of the presence of HPV DNA in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy. In this report the preliminary results of this larger study are presented by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 44 patients with cervical carcinoma. Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51. Clinical and histopathologic data of these patients was analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 24 (54.6%) patients, while local extension to vagina and parametrial tissues was found in 6 (13.6%) and 14 (31.8%) patients, respectively. Pelvic lymph node involvement was found in 15 (34%) patients. During the follow up period (range, 2-72, mean, 39 months), recurrences were observed in 6 patients. HPV DNA was detected in 20 (45%) cervical carcinoma specimens. The prevalence rate of different HPV types was 34% (18) for HPV 16/18, 9% (4) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate in relation to the presence of HPV DNA exhibited a trend but was not statistically significant. Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 5% (1 case), compared to 21% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, histologic subtype, maximum depth of cervical stromal invasion, longitudinal tumor diameter, tumor-cervix area quotient, parametrial involvement, vaginal invasion, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, age) were also correlated with the presence of HPV. None of these factors was found to have statistically significant relationship to the presence of HPV DNA. The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be unrelated to recurrence rate and various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.