Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung

The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.     

NM23 GENE EXPRESSION IN GASTRIC CARCINOMA: AN IMMUNOHISTOCHEMICAL STUDY

Background : The gene Nm23 is thought to play a role in the suppression of tumour metastasis. Reduced expression of Nm23 is seen in a number of human cancers, and is associated with increased metastasis and reduced survival, most strongly in ductal breast and colorectal carcinomas. Methods: Nm23 gene expression was compared in gastric carcinoma and normal gastric mucosa. Twenty-three gastric carcinomas were graded for differentiation as either well, moderately or poorly differentiated. Metastatic deposits from seven of the cases were also examined, along with 10 samples of normal gastric mucosa. Specimens were incubated with a murine monoclonal antibody against the protein product of Nm23, and examined by immunohistochemical staining. A semiquantitative immunostaining index was used. Results: All normal mucosa showed moderate to strong staining; 8 of 15 poorly differentiated carcinomas showed absent or weak staining; 1 of 6 moderately differentiated carcinomas stained weakly. Both well-differentiated carcinomas stained strongly; 1 of 7 metastatic deposits stained weakly. The difference in Nm23 expression between normal mucosa and carcinomas was statistically significant (P= 0.024). However, there was no statistically significant difference between the three grades of carcinomas (P= 0.51), or between primary and metastatic tumour (P= 0.25, all by Chi-squared test). Conclusions : These results suggest that Nm23 may have a role in gastric carcinoma pathogenesis, but do not show a correlation with metastasis. A larger study, involving detailed clinical staging and follow-up, may be of benefit.     

Comparative morphometric evaluation of microvessel density and nuclear area in ductal carcinoma in situ and hyperplastic ductal breast lesions

Tumour angiogenesis, as assayed by microvessel density, has been proposed as a prognostic factor in invasive breast cancer. Angiogenesis in noninvasive tumours and hyperplastic mammary lesion has not been well-established. The aim of the present study was to evaluate the microvessel density in ductal proliferative breast lesions and to investigate the relationships between microvessel density and histopathologic features. In addition, morphometric measurement of nuclear area in ductal proliferative breast lesions and its relationship with microvessel density has been examined. Thirty-four cases were evaluated, 19 ductal carcinomas in situ (DCIS) and 15 of usual and atypical ductal hyperplasias. Formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin-eosin, Feulgen, and then immunostained with an endothelial cell marker (anti-CD34). We utilized a CUE-2 (Olympus) Image Analysis System for morphometric analysis. In each case, microvessels surrounding involved spaces within the fields having the greatest vascularization were then counted.There was a statistically significant association between microvessel count and nuclear area, and between each of them separately with histological features. Moreover, two different distribution patterns of stromal microvessels, in DCIS and ductal hyperplastic epithelial lesions, were distinguished. In conclusion, our findings show an increase in blood vessel density and mean nuclear area from ductal hyperplasia to poorly differentiated DCIS, which is statistically significant.     

Neuroendocrine differentiation in "poorly differentiated" colon carcinomas

The diagnosis of "poorly differentiated" carcinoma was made in 47 of 683 colon cancers on the basis of conventional light microscopy which showed poorly defined glands, solid architecture or variable admixtures thereof. Samples from 44 of these 47 tumors were assessed by immunohistochemical analysis for the presence of neuroendocrine (NE) antigens. Paraffin sections were immunostained with antibodies to NSE, chromogranin, serotonin, VIP, substance P and somatostatin. Additional sections were also stained with monoclonal antibody (Mab) A-80 that recognizes a glycoprotein related to exocrine (EX) differentiation. Based on our findings, the tumors were phenotypically reclassified as follows: I) pure EX (n = 8), II) pure NE (n = 4), III) mixed EX-NE carcinomas (n = 23), and IV) predominantly EX carcinomas with occasional NE cells (n = 9). Survival among groups II and III appeared to be less than group I and survival in group IV was significantly less than group I. Survival among the four pure NE (group II) and 11 predominantly NE mixed carcinomas (group III) taken together was significantly less than the pure EX carcinomas. This study indicates: 1) The incidence of NE differentiation in tumors of the colon and rectum is higher than previously believed. 2) The poorly differentiated colon carcinomas comprise four distinct groups: pure EX, pure NE, mixed EX-NE carcinomas, and predominantly EX carcinomas with a NE cell subpopulation. 3) The presence of NE differentiation or of a NE cell subpopulation in colon carcinoma appears to be associated with a poorer prognosis.     

Pathologic characteristics of NUT midline carcinoma arising in the mediastinum

NUT midline carcinomas (NMCs) comprise a group of highly aggressive tumors that have been reported primarily in the head, neck, and mediastinum of younger individuals. These tumors overexpress the nuclear protein in the testis (NUT), most commonly due to a chromosomal translocation that fuses the NUT gene on chromosome 15 with the BRD4 gene on chromosome 19. Although the earliest recognized cases were described in the thymus or mediastinum, an extensive survey for NMCs among malignant thymic or other mediastinal neoplasms has not been reported. We examined NUT expression in 114 cases of poorly differentiated carcinomas or unclassified mediastinal malignancies using a clinically validated NUT-specific monoclonal antibody. Four of 114 (3.5%) cases showed nuclear NUT expression. A NUT translocation was confirmed by fluorescence in situ hybridization in 3 of these cases. These tumors arose in 2 men and 2 women with a median age of 50 years (range, 28 to 68 y). Three of the tumors were originally diagnosed as undifferentiated epithelioid or round cell malignant neoplasms; 1 tumor contained focal squamous differentiation and was originally diagnosed as a poorly differentiated squamous carcinoma of probable thymic origin. We find that the incidence of NMC within the mediastinum, particularly among undifferentiated tumors, is similar to that reported at other anatomic sites. NMC should be considered in the differential diagnosis of any poorly differentiated epithelioid mediastinal tumor, regardless of age.     

DNA pattern and cytological findings in fine-needle aspirates of untreated prostatic tumors. A flow-cytofluorometric study

The cellular DNA content in fine-needle prostatic aspirates from 500 untreated patients was determined by flow cytofluorometry. According to the DNA patterns diploid, tetraploid, and non-tetraploid aneuploid cases were identified. In 301 cytologically benign cases more than 90% showed diploid DNA patterns. Among 166 carcinomas the incidence of aneuploid DNA values increased with the degree of anaplasia, ie, 44% in well-differentiated, 78% in moderately differentiated, and 97% in poorly differentiated tumors. In aneuploid cases of well-differentiated carcinomas almost exclusively tetraploid DNA patterns were observed, while in poorly differentiated carcinomas about 80% showed non-tetraploid aneuploid DNA distributions. Among aneuploid cases of moderately differentiated carcinomas 2/3 were tetraploid and 1/3 non-tetraploid aneuploid. Morphologically similar tumors may thus be separated by the DNA profiles. The biological significance of these results must be further evaluated by clinical follow-up of the patients.     

Plastic-embedded endoscopic biopsies. Diagnostic advantages

As the use of endoscopic biopsy has increased in recent years, the pathologists whose job it is to interpret these small specimens have been asked to give more specific diagnoses. Plastic embedding has proved to be a useful diagnostic tool because it provides better morphology than routine paraffin embedding and because enzyme histochemical and immunohistochemical markers can be used. We applied these techniques to endoscopic biopsies hoping to increase the diagnostic yield. Biopsies from 75 patients were fixed in paraformaldehyde, embedded in methacrylate, and sectioned at 2 mu. These sections were then compared with routine sections from the same patient. Additional special stains were used and enzyme histochemistry, or immunohistochemistry was performed on the plastic- or paraffin-embedded tissue as needed. We found that in 26.7% of the cases, plastic sections resulted in more specific diagnoses than was possible with paraffin sections. When distinguishing lymphomas from poorly differentiated carcinomas, this method provided much better morphologic differentiation and better demonstration of leukocyte common antigen than keratin staining. Identification of B- or T-cell antigens was possible on plastics but not on paraffin. Furthermore, lesions such as histiocytosis X and cryptosporidiosis were more accurately identified. Thus, we found that the plastic-embedded tissue provided all the information yielded by routine paraffin embedding and also improved the diagnostic yield on certain types of neoplastic or infectious processes.     

Immunohistochemical demonstration of tumor-associated antigens in prostatic carcinomas of various histological differentiations

Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP.     

Centrally necrotizing carcinomas of the breast: a distinct histologic subtype with aggressive clinical behavior

Most breast carcinomas exhibit ductal differentiation. However, recognition of less common histologic patterns provides clinically useful data. This report describes a distinctive subtype of breast carcinoma that we have termed "centrally necrotizing carcinoma" (CNC; in this study, N = 34), which is characterized by an unusual and aggressive natural history. Centrally necrotizing carcinomas are composed of well-circumscribed, unicentric nodules with extensive central necrosis that are surrounded by a narrow rim of viable high-grade tumor cells. These tumor cells show minimal ductal differentiation (i.e., tubule formation), but are usually associated with focal ductal carcinoma in situ. The mean age of the patients in this study was 57.5 +/- 11.6 years, and the mean tumor size was 2.5 +/- 1.2 cm. Twenty-eight percent of the patients had positive axillary lymph nodes (mean number of lymph nodes involved, 2.1 +/- 1.2). Ninety-four percent of cases were negative for estrogen and progesterone receptors. In 21 patients (62%), local and/or distant recurrences developed (median time to recurrence, 16.2 months), and, to date, 20 have died from breast cancer (median time to death, 22.5 months). Progression of disease (defined as the development of either a recurrence or death resulting from disease) occurred in 24 patients (71%). Comparison with a set of 26 poorly differentiated ductal carcinomas with (nonextensive, patchy) necrosis matched for age, tumor size, and lymph node status showed a significantly worse progression-free survival rate for the CNC group (p < 0.004). We conclude that CNC is an uncommon but readily identifiable subtype of breast carcinoma and is characterized by early systemic metastasis and an accelerated clinical course.     

Diagnostic value of histochemistry in embryonal rhabdomyosarcoma.

Embryonal rhabdomyosarcomas from the nasopharynx of two children were examined by histochemical methods commonly applied to muscle biopsies. These stains included nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR), succinate dehydrogenase (SDH), PAS, PAS-diastase, myophosphorylase, calcium-mediated adenosine triphosphatase (ATPase) preincubated at high and low pH, and oil red O. Myofibrils were easily identified with ATPase and blood vessel walls were also stained. NADH-TR clearly showed longitudinal and cross-striations that were not seen with H&E or PTAH stains. The modified Gomori trichrome stain additionally contributed to the recognition of myofibrils. Some techniques of muscle histochemistry applied to fresh frozen sections of tumor tissue may provide evidence of muscular differentiation in otherwise poorly differentiated sarcomas for a more accurate diagnosis of rhabdomyosarcoma.     

Adenosquamous cervical carcinoma morphological characteristics

Adenosquamous carcinomas range between 5-25% of cervical cancers and are composed by an admixture of malignant squamous and glandular elements. The aim of our study was to identify some common characteristics and to evaluate the correlation between the degrees of differentiation of the two components. We analyzed 15 cases diagnosed in a 6 years period. The age ranged between 26 years and 67 years (mean age 46.5 years). Paraffin embedding, followed by HE staining were performed. Differential diagnosis with endometrioid adenocarcinoma of the cervix with squamous metaplasia was made. Four cases (26.66%) were subtyped as clear cell adenosquamous carcinomas and 2 cases (13.33%) were subtyped as glassy cell carcinomas, exhibiting finely granular ground glass type cytoplasm. 93.33% of cases exhibited a poorly differentiated squamous component and 66.66% of cases exhibited a well differentiated glandular component. 20% (3 cases) presented prominent lymphoplasmacytic and eosinophilic inflammatory tumoral infiltrate. Squamous intraepithelial lesions in overlying epithelium was observed in 4 cases (26.66%). One case presented extension to the uterine body. One case, diagnosed as glassy cell subtype, presented regional lymph node metastases. Our study concluded the occurrence of adenosquamous cervical carcinomas at a similar age with squamous cervical carcinomas in the investigated group of patients. As adenosquamous cervical carcinomas are considered expressions of a biphasic differentiation of a single pluripotential sub-columnar reserve cell, a similar degree of differentiation of the two components would be expected. Although, we registered a degree of variability in grading of the two components, with a tendency of squamous component toward poorly differentiated aspect and a slightly dominant aspect of well differentiated glandular pattern.     

Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis

Inverted papilloma of the urinary bladder and urothelial carcinoma with an inverted (endophytic) growth pattern may be difficult to distinguish histologically, especially in small biopsies. The distinction is important as these lesions have very different biologic behaviors and are treated differently. We examined histologic features and undertook immunohistochemical staining and UroVysion fluorescence in situ hybridization (FISH) to determine whether these methods could aid in making this distinction. We examined histologic sections from 15 inverted papillomas and 29 urothelial carcinomas with an inverted growth pattern. Each tumor was stained with antibodies to Ki-67, p53, and cytokeratin 20. In addition, each tumor was examined with UroVysion FISH for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 signals. None of the inverted papillomas stained positively for Ki-67 or for cytokeratin 20. Only 1 of 15 inverted papillomas stained positively for p53. By contrast, 66%, 59%, and 59% of urothelial carcinomas with an inverted growth pattern stained positively for Ki-67, p53, and cytokeratin 20, respectively. Only 3 of the urothelial carcinomas stained negatively for all 3 immunohistochemical markers. UroVysion FISH produced normal results for all cases of inverted papilloma. By contrast, 21 of 29 cases (72%) of urothelial carcinoma with an inverted growth pattern demonstrated chromosomal abnormalities typical of urothelial cancer and were considered positive by UroVysion FISH criteria. Morphologic features, as well as immunohistochemical stains (including stains for Ki-67, p53, and cytokeratin 20) and/or UroVysion FISH can help to distinguish inverted papilloma from urothelial carcinoma with an inverted growth pattern.     

Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6

The availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinomas (NSCLCs). The aim of this study was to assess the utility of immunohistochemical markers in subtyping poorly differentiated NSCLC and to compare the results of immunohistochemical staining on biopsies with the corresponding resections. Thirty-nine cases of NSCLC that could not be further classified on biopsy and had subsequent resection specimens were identified. Classification of the tumor was based on the resection specimen using the World Health Organization criteria. All biopsies and resections were stained with CK7, TTF-1, napsin A (novel aspartic proteinase of the pepsin family), p63, CK5/6, and 34βE12. The specimens included 20 adenocarcinomas (ACs), 15 squamous cell carcinomas (SCCs), and 4 large-cell carcinomas (LCCs). TTF-1 was positive in biopsies from 16 of 20 ACs, 2 of 4 LCCs, and none of the SCCs. p63 was positive in all 15 SCCs, 2 of 20 ACs (both were also positive for TTF-1 and napsin A), and none of the LCCs. CK5/6 was positive in 11 of 15 SCCs (all p63 positive) but none of the ACs or LCCs. Napsin A stained 11 of 19 ACs (all TTF-1 positive) but none of the other tumors. Staining for CK7 was present in 19 of 19 ACs and 9 of 15 SCCs. 34βE12 stained both SCCs (15 of 15) and ACs (12 of 20). The combination of TTF-1, napsin A, p63, and CK5/6 allowed an accurate classification of 30 of39 (77%) cases. Of 232 pairs of slides (biopsy and resection) stained with immunohistochemical markers, 12 (5%) showed discrepancies in immunohistochemical staining between biopsies and their corresponding resections. Immunohistochemical staining using a combination of TTF-1, napsin A, p63, and CK5/6 allows subclassification of poorly differentiated NSCLCs on small lung biopsies in most cases. Discrepancies in immunohistochemical staining between biopsies and resections are uncommon.     

Subdividing ovarian and peritoneal serous carcinoma into moderately differentiated and poorly differentiated does not have biologic validity based on molecular genetic and in vitro drug resistance data

Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinomas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.     

Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma.

Primary adenocarcinoma of the urinary bladder sometimes causes a diagnostic dilemma because it can be indistinguishable morphologically from adenocarcinoma of colorectal origin secondarily involving the bladder by metastasis or direct extension. It is much less well studied than conventional urothelial carcinoma and colorectal adenocarcinoma because of its rarity. The current study was specifically designed to investigate whether an important mechanism involved in the pathogenesis of colorectal adenocarcinoma, beta-catenin dysregulation, was also important for the development of primary bladder adenocarcinoma and whether these two morphologically similar tumors could be distinguished immunohistochemically. Formalin-fixed, paraffin-embedded tissues from 17 primary adenocarcinomas of the urinary bladder, 16 colorectal adenocarcinomas involving the bladder, and 10 conventional urothelial (transitional) carcinomas were included in this study. Thirteen of the primary bladder adenocarcinomas were moderately to well differentiated (enteric type) and morphologically indistinguishable from colorectal cancers. The remaining four primary tumors were poorly differentiated (two cases) or of clear cell type (two cases). Immunohistochemical studies using a panel of monoclonal antibodies demonstrated positive nuclear staining for beta-catenin expression in 13 of the 16 (81%) colorectal adenocarcinomas secondarily involving the bladder but in none of the primary adenocarcinomas or the urothelial carcinomas. Instead, positive membranous (and some cytoplasmic) staining was present in all primary bladder tumors with the exception of two poorly differentiated adenocarcinomas where no beta-catenin staining was detected. All secondary colorectal adenocarcinomas stained negatively for CK7 and thrombomodulin (TM), whereas positivity for CK20 was observed in 15 (94%) cases. All urothelial carcinomas stained positively for CK7 and TM, and four of them also for CK20. Primary adenocarcinomas of the bladder showed mixed staining patterns for CK7, CK20, and TM with a positive rate of 65%, 53%, and 59%, respectively. These data indicate that dysregulation of beta-catenin, an important aberration seen in colorectal carcinogenesis, does not appear to play a role in the pathogenesis of the bladder adenocarcinoma. In addition, our data demonstrate that a panel of immunostains, including CK7, CK20, TM, and beta-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.     

Morphologic and cell kinetic studies of prostate cancers. Contribution to grading

The combined histologic and cytologic grading of carcinomas of the prostate is not only important in evaluation of prognosis but determines the choice of therapy with knowledge of staging. Tissue biopsies of 2,200 prostatic carcinomas were classified and graded histologically and cytologically. Furthermore, autoradiographic studies were performed on 69 needle biopsies with 3H-thymidine. The cytologic parameters were correlated with cell-kinetic parameters in classification. Several subgroups of degrees of malignancy were found. Grade Ia corresponds to highly differentiated glandular carcinomas by histology and cytology. Grade Ib carcinomas were histologically well but cytologically moderately differentiated. Grade IIa carcinomas are histologically moderately to poorly but cytologically moderately differentiated. Grade IIb carcinomas correspond to poorly differentiated tumors by histological and cytological criteria. Grade III carcinomas are in most cases undifferentiated. This differentiated grading is particularly important for therapeutic consequences in incidental carcinomas. The therapeutic consequences of grade Ia carcinomas are frequent controls and a wait-and-see attitude. Grade Ib and IIa carcinomas must be treated according to their clinical stage by total prostatectomy. Grade IIb and III carcinomas need a palliative treatment by hormones, castration, irradiation or cytostatic drugs.     

Expression of RON Proto-oncogene in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma

Recently, it was reported that RON proto-oncogene, encoding a receptor tyrosine kinase, was strongly expressed in renal oncocytomas but not in any renal cell carcinomas, including 5 chromophobe renal cell carcinomas, which morphologically resemble oncocytomas. To determine its diagnostic value, we studied Ron protein expression by immunohistochemistry in a larger number of renal cell neoplasms with emphasis on chromophobe renal cell carcinomas. Tissue microarrays containing 141 renal cell neoplasms, including 55 oncocytomas and 52 chromophobe renal cell carcinomas, were constructed. In addition, conventional sections from 15 cases of oncocytoma and 5 cases of chromophobe renal cell carcinoma were analyzed. Immunohistochemistry was carried out with a monoclonal mouse anti-human Ron-alpha antibody. Staining intensity was scored on a 0 to 3 scale. Ninety-nine percent of oncocytomas (69 of 70) and 96% of chromophobe renal cell carcinomas (55 of 57) showed moderate to strong, diffuse cytoplasmic Ron immunoreactivity with intensities > or =2, while only 17% of other renal cell carcinoma subtypes stained with intensities > or =2. Our study indicates that Ron immunostaining cannot be used to distinguish oncocytoma from chromophobe renal cell carcinoma.     

A clinical study of prostatic carcinoma

Seventy seven patients with prostatic carcinoma were treated in our clinic between 1977 and 1986. Most of them were treated by a hormonal agent as the first therapy. None of the 9 stage A1 cases showed any reactivation, but 4 of the 5 stage A2 cases relapsed to metastatic disease. The chemotherapy performed in 3 of the 4 reactivated cases had no obvious effect on the disease. Seven of the 8 patients with stage B disease were alive without relapse. Relapse was seen in the other patient who had poorly differentiated carcinoma and chemotherapy in this case resulted in stable disease for the present. Four of the 15 stage C cases including 3 poorly differentiated carcinomas were hormone resistant or reactivated. For these resistant cases radiotherapy and/or the chemotherapy were performed, but a response was seen in only one case. Consequently, the first therapy for stage A2, B and C of poorly differentiated carcinoma must be improved. Of the 40 stage D cases, 4 patients who were treated by an early combination of hormonal therapy and chemotherapy had a better prognosis than the others. These 4 patients had poorly differentiated carcinomas with multiple bone metastases. Two of these 4 patients were alive without relapse for 17 and 72 months, and one of the 2 patients with relapse was also alive for 75 months. We believe that early chemotherapy is the key for better prognosis in stage D cases.     

Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands

Mucins are glycoproteins normally synthesized by a variety of secretory epithelial cells. The aim of this study was to investigate the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUCB, MUC6, MUC7) in mucoepidermoid carcinomas, the most frequent malignant tumor of salivary glands. Forty mucoepidermoid carcinomas and twenty-two normal salivary glands were studied for these mucins by immunohistochemistry from formalin-fixed and paraffin-embedded material. Normal salivary glands frequently expressed MUC1 and MUC4, mainly in ductal cells; MUC5B and MUC7 stained mucous and serous acini respectively of submandibular and minor salivary glands; and MUC5AC and MUC2 were poorly detected in excretory ducts. All mucoepidermoid carcinomas expressed MUC1, and 38/40 tumors expressed MUC4. Both membrane-bound mucins stained membranes and cytoplasm of all cell types (epidermoid, intermediate, mucous, clear and columnar). MUC5AC and MUC5B stained glandular differentiated cells in most tumors (29/40 and 33/40 cases, respectively). MUC6 was positive in 13/40 tumors, and both MUC2 and MUC7 in only 2/40 tumors. The high expression of MUC1 was related to high histologic grades, high recurrence and metastasis rates and a shorter disease-free interval (P < 0.05). Conversely, MUC4 high expression was mainly related to low-grade tumors, lower recurrence rates and a longer disease-free interval (P < 0.05). In conclusion, mucoepidermoid carcinomas of salivary glands usually express MUC1, MUC4, MUC5AC and MUC5B; less frequently MUC6; and rarely MUC2 and MUC7. This mucin expression pattern can be useful for diagnostic purposes. Therefore, MUC1 expression is related to tumor progression and worse prognosis, whereas MUC4 expression is related to a better prognosis.