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Biomedical subjects

G K Jacobsen

Publications and source records attributed to G K Jacobsen.

At least 37 records · Page 2Linked to original sources

Comparison of two monoclonal antibodies for the detection of estrogen receptors in primary breast carcinomas.

A new monoclonal antibody against estrogen receptor (ID5, Dako) has shown promising results when applied to formalin fixed, paraffin embedded tissue. In order to determine whether this antibody can compete in specificity and sensitivity with the ER-ICA antibody (Abbott Laboratories), a comparative, prospective study of the two antibodies was carried out on paraffin embedded and fresh frozen tissue in three laboratories. Two hundred and fifteen breast carcinomas were examined. Formalin fixed, paraffin embedded tissue was available from 215 tumors, and fresh frozen tissue from 189 of the tumors. Of these, 124 tumors were also investigated by the enzyme-linked immunosorbent assay. The results from each of the three laboratories correspond with those obtained for the whole material. The percentage of tumors positive for estrogen receptors within the different methods, was as follows: 71% by ID5 on paraffin sections, 50% by ER-ICA on paraffin sections, 65% ER-ICA on frozen sections and 88% by the EIA. When comparing the different immunohistochemical results and the EIA in 2 x 2 tables, agreement was reached in 69% to 91% of the cases. The best agreement (91%) was found between results obtained with the ID5 antibody used on formalin fixed, paraffin embedded tissue and the ER-ICA kit used on fresh frozen tissue. The advantages of using the ID5 antibody are associated with its applicability to formalin fixed, paraffin embedded tissue: improved morphology, reproducibility, retrospective studying and low costs. Finally, it is reproducible not only within the same laboratory but also among different laboratories.

Antibodies, Monoclonal↗

Endoscopic ultrasonography and real-time guided fine-needle aspiration biopsy of solid lesions of the mediastinum suspected of malignancy.

STUDY OBJECTIVE: The study details our preliminary experience with endoscopic ultrasonography (EUS) guided fine-needle aspiration biopsy (FNAB) of mediastinal masses suspected of malignancy. DESIGN: Prospective uncontrolled study. PATIENTS: Nine patients had lesions suspected of malignancy ranging from 1 to 9 cm in diameter in various locations of the mediastinum. INTERVENTIONS: The EUS examination was performed with a gastroscope (Hitachi/Pentax FG-32 UA) equipped with an adjustable 5- or 7.5-MHz curved array ultrasonic transducer. The scanning plane is in the long axis of the endoscope allowing endosonographically guided biopsy to be performed. A 21-gauge (0.8 mm), full-length steel needle housed in a biopsy handle (type: Hancke/Vilmann; GIP-Medizin Technik; Grassau, Germany) was used for the biopsies. RESULTS: Nine patients had biopsy specimens taken from 13 lesions. The total number of needle passes was 18 (range, 1 to 3; median, 1.4). The cytologic diagnosis was conclusive for cancer in ten lesions and consistent with a benign lesion in three lesions. All ten malignant diagnoses and two benign diagnoses were confirmed either by operation or follow-up. In the last patient with lung cancer, a final diagnosis of the EUS-guided biopsy of an enlarged lymph node could not be obtained. No false-positive or negative biopsy diagnoses were recorded. The biopsy procedure was well tolerated by all patients, and there were no complications. CONCLUSIONS: EUS-guided aspiration biopsy is a significant advance in the differentiation between malignant and benign lesions of the mediastinum carrying a high diagnostic potential.

Aged↗

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

Animals↗

Growth of vestibular schwannomas: in situ model employing the monoclonal antibody Ki-67 and DNA flow cytometry.

Vestibular schwannoma (VS) growth potentials were studied in an in situ model, in which the cycling cellular fraction was determined immunohistochemically by applying the mouse monoclonal Ki-67 antibody, and the tumor ploidy was estimated by DNA flow cytometry in a consecutive series of 124 VSs. The tumors were classified according to the average number of positively stained nuclei in 10 high-power fields into three groups: 28 highly (> 10), 33 moderately (> 5-10) and 63 low proliferating (< or = 5). The intratumoral proliferative variation was studied in 10 tumors. Only slight variation in the number of the positively stained nuclei were observed. Six of seven tumors removed because of macroscopically documented growth by computed tomography (CAT) scan were moderately or highly proliferative. Proliferation of VS was correlated to prospectively registered clinical data. A statistically significant relation was found between VS proliferation and the prediagnostic duration of symptoms (p = 0.0001). The proliferative status was unrelated to age, sex, and tumor size. Flow-cytometric determination of DNA index of the 124 tumors revealed 12 tetraploid (DNA index = 2), 110 diploid (DNA) index = 1) and two nondiploid tumors. A statistically significant relation was noted between tumor ploidy and proliferation status expressed by Ki-67 (p = 0.024). The tetraploid tumors showed significantly lower proliferation compared with the diploid tumors. Tumor ploidy was statistically unrelated to age, sex, tumor size, and duration of symptoms. The results of this study provide a link between the immunohistochemical, flow cytometric findings, and clinical data, which could probably be relevant in identifying patients at risk for rapid tumor growth and tumor recurrences, because a rapid test for cell proliferation is now available.

Adult↗

An immunohistochemical study of p53 with correlations to histopathological parameters, c-erbB-2, proliferating cell nuclear antigen, and prognosis.

In an immunohistochemical study of 490 primary breast cancer patients with a follow-up period of more than 10 years, we found that p53 was not a prognostic factor for disease-free or overall survival among the whole cohort or among lymph node-positive or -negative patients. In a multiple logistic regression model classical histopathological parameters, such as lymph node status, number of mitoses, histological grade, and absence of progesterone receptors, were independent, poor prognostic predictors. In univeriate analysis p53 immunoreactivity was positively correlated with the absence of tubule formation, high histological grade (poor differentiation), absence of estrogen receptors (ER), and a high proliferating cell nuclear antigen (PCNA) score (ie, parameters indicative of an aggressive phenotype). The lack of prognostic significance may be attributable partly to the method used, because immunohistochemistry underdetects rather than overdetects p53 protein. No correlation between p53 and c-erbB-2-oncoprotein was demonstrated.

Adult↗

Immunohistochemical study of estrogen receptors in primary breast carcinomas and their lymph node metastases including comparison of two monoclonal antibodies.

Estrogen receptors (ER) status was investigated in 101 primary breast carcinomas and their axillary lymph node metastases to determine if the malignant cells retained or changed this phenotypic feature during the metastatic process. Immunohistochemistry with the ER-ICA kit (Abbott Laboratory) on formalin-fixed paraffin-embedded tissue was used (paraffin ER-ICA). The ER status in primary and secondary tumours was concordant in 80 patients (79%) and discordant in 21 (21%). Eighteen of these twenty-one patients had ER-positive primary tumours and ER-negative lymph node metastases. This discordance, which may be due to loss of ERs in the metastatic cells or tumour heterogeneity, could explain the well-known failure of endocrine treatment in some of the patients with ER-positive primary tumours. A new monoclonal antibody ID5 (DAKO) against ERs was applied on formalin-fixed paraffin-embedded tissue from 83 of these 101 primary carcinomas. These analyses and paraffin ER-ICA analyses were compared to prior analyses of the same 83 tumours using the ER-ICA kit on fresh frozen tissue ("gold standard", frozen ER-ICA). Kappa coefficient, sensitivity and specificity were 0.74, 0.96 and 0.75 for ID5 antibody, and 0.59, 0.72 and 0.96 for ER-ICA antibody on paraffin sections.

Antibodies, Monoclonal↗

The prognostic significance of immunohistochemically detectable metallothionein in primary breast carcinomas.

Metallothionein (MT) is a low-molecular-weight protein with a high affinity for group II metal ions, especially zinc and copper. MT serves as an intracellular reservoir of these ions, but may also be involved in the detoxification of certain toxic metal ions such as cadmium. In addition, high MT contents might protect tumour cells from alkylating agents and irradiation. The aim of this study was to evaluate the prognostic significance of immunohistochemically detected MT overexpression in patients with primary breast carcinoma: 478 patients with primary breast carcinoma diagnosed during the period 1980-1985 were included. Formalin-fixed and paraffin-embedded tissue was used. Immunoreactivity for MT was found to be independent of the length of formalin fixation if the sections were microwave processed before incubation with the primary antibody. Patients were divided into two groups: those with MT overexpression (more than 10% positive tumour cells) and those with low expression (less than 10% positive tumour cells). MT overexpression was correlated with postmenopausal status, large tumour size, presence of lymph node metastases, high number of mitoses, severe nuclear pleomorphism, high histological grade (poor differentiation), and absence of PgR. In univariate analysis of survival data, MT overexpression was a predictor of poor overall survival in the entire group of patients. In multivariate analysis, MT overexpression failed to be of prognostic significance, whereas classical histopathological parameters such as tumour size, histological grade, and PgR were of independent prognostic significance.

Analysis of Variance↗

Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction.

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.

Carcinoma, Squamous Cell↗

Immunohistochemical detection of p53 in epidermal proliferations overlying dermatofibromas.

Basaloid proliferations of epidermis overlying dermatofibromas and morphologically resembling superficial basal cell carcinomas might possess a malignant potential. In order to elucidate whether these basaloid proliferations share phenotypic characteristics with malignancy, we examined immunohistochemically 19 cases of dermatofibroma with overlying epidermal basaloid proliferations, 10 dermatofibromas with overlying simple epidermal proliferations, and 10 invasive basal cell carcinomas for expression of p53. Simple and basaloid proliferations showed sparse positive immunostaining for p53, as seen in normal epidermis. No differences in staining pattern or number of positive keratinocytes could be demonstrated between these conditions. The dermatofibromas were negative. The invasive basal cell carcinomas showed abundant p53 positivity. The lack of p53 immunoreactivity in the epidermal basaloid proliferations overlying dermatofibromas indicates that these lesions have not acquired a phenotype as seen in malignant conditions.

Basal Cell Carcinoma↗

Bronchoalveolar lavage in radiologically detected diffuse lung disease. Diagnostic value of total and differential cell count in a series of 130 patients.

During a 7-year period bronchoalveolar lavage (BAL) was performed as a routine diagnostic procedure at fiberoptic bronchoscopy in 172 consecutive patients with diffuse pulmonary lesions. In 42 patients, BAL was technically insufficient or data were incomplete. These patients were excluded. The remaining 130 patients consisted of 78 men and 52 women with a median age of 43 years (range 19-79); 59 were smokers. They were divided into 6 groups: I. sarcoidosis (n = 77); II. cryptogenic fibrosing alveolitis (n = 16); III. secondary fibrosing alveolitis (n = 7); IV. malignancy (n = 7); V. allergic alveolitis (n = 6); VI. miscellaneous (n = 17). Group VI was not included in the statistical evaluation, which involved only the 113 patients in groups I-V. BAL was performed in a segment of the right middle lobe with 150-200 ml isotonic saline. The return fluid (BALF) was filtered through two layers of cotton gauze, and total and differential cell counts were assessed. Median BALF return volume was 67% (range 35-90). Eighty percent of the procedures were performed by the same operator. Total cell count displayed no significant difference amongst the five diagnostic groups (p = 0.06). Differential cell count displayed differences amongst the groups respecting macrophages (p = 0.002), lymphocytes (p = 0.0004), neutrophils (p = 0.0001) and eosinophils (p = 0.04). Patients with sarcoidosis had a higher percentage of lymphocytes, patients with secondary fibrosis a higher percentage of neutrophils, and patients with cryptogenic fibrosis a higher percentage of eosinophils than the other groups. Malignant cells were observed in BALF in 14.3% of patients with malignant lesions. Among the patients with sarcoidosis, 75% had a lymphocyte-dominated BALF (> 10%) compared with 31% of the patients with cryptogenic fibrosis, 14% of the patients with secondary fibrosis, and 43% of the patients with malignancy. Dominance of neutrophils (> 10%) and/or eosinophils (> 5%) in BALF was observed in cryptogenic and secondary fibrosis. In most patients, BAL cannot provide a definite diagnosis, but may support the clinical suspicion of a specific diagnosis. In clinical practice, BAL seems to be of limited value in the diagnostic evaluation of radiologically detected diffuse, non-infectious pulmonary lesions.

Adult↗

[Disseminated primary bronchogenic carcinoma in 3 young patients].

Primary lung cancer in young patients is rare, patients under 40 years of age constituting between 1.2 and five percent of all cases. Three cases of primary lung cancer in young patients are presented, and the typical manifestations of primary lung cancer in young patients are discussed.

Adult↗

[Increased incidence of sarcoma in patients treated for seminoma].

In a nationwide cancer registry analysis of second primary malignancies in 6187 men with testicular cancer in the period 1943-1987, 13 sarcomas were found, yielding a 4-fold increase of the relative risk (RR). The majority of sarcomas occurred in men with seminoma, and the increased incidence was seen irrespective of time since the diagnosis of testicular cancer. The interval between the testicular cancer and the sarcoma varied from five to 34 years. After investigation of the hospital records and re-examination of the histological specimens, three patients were excluded. In spite of this, the RR was still considerably increased (at least three-fold). Seven of the 10 sarcomas were found to be located within the field of the radiation treatment administered and three at the periphery. The histological type of sarcomas varied, with leiomyosarcoma as the most frequent (three cases), followed by malignant fibrous histiocytoma (two cases) and fibrosarcoma (two cases). Since none of these patients had received chemotherapy and did not harbour sarcomatous components within the primary testis cancer, the sarcomas were probably caused by the radiation treatment. The absolute number of these secondary sarcomas is low, but the risk of developing such neoplasms and other malignancies should, even so, be kept in mind in the follow-up of testicular cancer patients.

Adolescent↗

Proliferating cell nuclear antigen in breast carcinomas. An immunohistochemical study with correlation to histopathological features and prognostic factors.

Proliferating cell nuclear antigen (PCNA), was examined by immunohistochemistry in 509 breast carcinomas. The immunoreactivity was found to be independent of the length of fixation when the tissue sections were microwaved before incubation with the primary antibody. The PCNA immunoreactivity was assessed by two semi-quantitative methods, which were correlated but not exchangeable. The comedo type of intraductal carcinomas and invasive ductal carcinomas had a higher PCNA score than other types. Lymph node metastases had a significantly higher PCNA score than primary carcinomas. High PCNA immunoreactivity was correlated with the presence of lymph node metastases, absence of tubule formation, numerous mitoses, severe nuclear pleomorphism, high histological grade and absence of progesterone receptors (PgR). PCNA in lymph node positive tumours was correlated with tumour type, especially with ductal carcinomas, absence of tubule formation, high histological grade and absence of PgR, whereas PCNA in lymph node negative tumours was correlated with large tumour size, numerous mitoses, severe nuclear pleomorphism and high histological grade. Number of mitoses and nuclear pleomorphism were the two most important factors in predicting the PCNA score; the absence of PgR and nuclear pleomorphism were important in lymph node negative and positive tumours, respectively. In a univariate analysis high PCNA score was found to be correlated with shorter relapse-free period and poorer over-all survival.

Breast Neoplasms↗

Examination for intratubular germ cell neoplasia at operation for undescended testis in boys.

A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including 1 nonseminoma of the contralateral testis, which had been treated before surgery for an undescended testis, 1 nonseminoma found at followup, 1 seminoma and 2 intratubular germ cell neoplasms. Of the later 3 patients 1 had a 45,X/46,XY karyotype and 2 had abnormal external genitalia. Previous testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia. The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood.

Biopsy↗

Microwave processing for immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded tissue.

The effect of microwave irradiation on the immunoreactivity of proliferating cell nuclear antigen (PCNA) in five primary breast carcinomas, a tonsil with hyperplasia, and a seminoma of the testis was evaluated in formalin-fixed and paraffin-embedded sections using the monoclonal antibody PC-10. The tissues were fixed in 4% buffered formaldehyde for 6, 24, 28, 72 h, and 1 week. Before incubation with the primary antibody, sections were microwaved for x2 5 min in distilled water, in citrate buffer, or they were processed routinely without microwave irradiation. In sections microwaved in distilled water the immunoreactivity was found to be independent of the length of fixation. PCNA immunoreactivity in sections microwaved twice in citrate buffer was not satisfactory. The PCNA immunoreactivity in sections which were routinely processed without microwave irradiation was markedly decreased after 48 h of fixation, and was nearly absent in sections fixed for up to 1 week. In sections processed without microwave irradiation the optimal dilution of the primary antibody was 1:10, whereas in sections microwaved twice in distilled water the optimal dilution was 1:600. The morphology of the tissue was well preserved after microwave processing. We therefore recommend microwave processing in distilled water for x2 5 min for demonstration of PCNA in formalin-fixed and paraffin-embedded sections using the monoclonal antibody PC-10, since this technique yields optimal staining reactions independent of the length of fixation.

Breast Neoplasms↗

c-erbB-2 oncoprotein is not an independent prognostic parameter in primary breast carcinoma. An immunohistochemical study.

The prognostic significance of c-erbB-2 oncoprotein expression was studied using the monoclonal antibody, anti-c-erbB-2 (CB-11, BioGenex) and the avidin-biotin-complex (ABC) technique. Four hundred and ninety patients with primary breast carcinoma diagnosed at Gentofte Hospital in the period 1980-1985 were included. Information about treatment, relapse-free period and overall survival was obtained from the Danish Breast Cancer Co-operative Group (DBCG). The mean follow-up period was more than 10 years. Fifteen per cent of the tumours showed positive immunoreactivity for c-erbB-2. Oncoprotein expression was correlated with presence of lymph node metastases, type of tumour, high number of mitoses, severe nuclear pleomorphism, high histological grade (poor differentiation), and absence of steroid hormone receptors. By univariate analysis, expression of c-erbB-2 oncoprotein, was correlated with poorer overall survival and shorter disease-free period in the entire cohort and in patients with lymph metastases, but not in the group of patients without lymph node metastases. By multivariate analysis, c-erbB-2 failed to be an independent prognostic marker for either disease-free period or overall survival, whereas classical histopathological parameters such as presence of lymph node metastases, high number of mitoses, high histological grade (poor differentiation) and absence of progesterone receptors turned out to be of independent prognostic significance.

Breast Neoplasms↗