Keratin expression in cervical cancer.

Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of detecting separately 11 subtypes of their epithelial intermediate filament proteins at the single cell level, we investigated keratin expression in 16 squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of the human uterine cervix. The keratin phenotype of the keratinizing squamous cell carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14, 16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases, usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16. Adenocarcinomas displayed a less complex keratin expression pattern comprising keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4, 5, 10 and 13 were sporadically found in individual cells in a few cases. These keratin phenotypes may be useful in differential diagnostic considerations when distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin 10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing carcinomas and poorly differentiated adenocarcinomas, which do not express keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of the cervix from those of the colon and also from mesotheliomas. Furthermore the presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive potential while its absence could be indicative of a regressive behavior. Because most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this expression pattern reflects the origin of cervical cancer from a common progenitor cell, i.e., the endocervical reserve cell that has been shown to express keratins 5, 8, 14, 17, 18, and 19.     

Expression of keratins 1, 6, 15, 16, and 20 in normal cervical epithelium, squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma.

Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition.     

Laminin and type VII collagen distribution in different types of human lung carcinoma: correlation with expression of keratins 14, 16, 17 and 18

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.     

Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.

AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia.     

Keratin expression in the normal anal canal

The pattern of epithelial keratin expression in the normal anal canal has not been extensively defined and is a necessary prerequisite to the interpretation of alterations in these intermediate filaments in pathological anal epithelial lesions. Thirty-five frozen tissue specimens of resected haemorrhoids were investigated immunohistolo-gically for expression of 14 individual keratins (K) using a panel of 17 monoclonal antibodies. Perianal skin showed basal expression of karatinocyte Ks 5, 14 and 17, and suprabasal expression of keratinocyte Ks 14, 10, 1 and 16. Anal squamous epithelium showed persistent basal K5 and 17, basal and suprabasal K4, 13 and 16 positivity, with sporadic expression of K1 and 10. The expression of simple epithelial keratins in squamous epithelium adjacent to the anal transitional zone varied with basal expression of K7, K8, K18 and K19 and sporadic suprabasal expression of K7 and K19. The anal transitional zone (ATZ) expressed K19, as found in transitional epithelia elsewhere. The full thickness of epithelium was positive for the simple epithelial Ks 7, 8 18 and 19. Marked heterogeneity of keratinocyte keratin expression was seen. Basal layers expressed Ks 4, 13, 14 and 17 and variably K16, while suprabasal layers expressed Ks4 and 13, 14 and 17 and variably K16, while suprabasal layers expressed Ks4 and 13 and variably K14, 16 and 17. This anomalous expression of keratinocyte K4 and 13 has also been documented in transitional epithelium of the bladder. The anal glands and ducts showed a keratin distribution similar to the transition zone. Rectal columnar epithelium expressed simple keratins 7, 8 18 and 19. In addition, low levels of keratinocyte keratins were found as indicated by heterogeneous staining for K4, 13, 14 and 16. The overall pattern, particularly in the region of the anal transitional zone and immediately adjacent squamous and columnar epithelia, is of a flexible epithelial cell population able to express a range of keratins unrestricted by a particular morphological phenotype. In the light of these results, analysis of changes in keratin distribution within anal carcinomas may assist classification by providing information on the state of differentiation and histogenesis of these tumours.     

Keratin expression profiling of transitional epithelium in the painful bladder syndrome/interstitial cystitis

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a severely debilitating condition. Its cause is poorly understood; therapy is symptomatic and often unsuccessful. To study urothelial involvement, we characterized the keratin phenotype of bladder urothelium in 18 patients with PBS/IC using a panel of 11 keratin antibodies recognizing simple keratins found in columnar epithelia (keratins 7, 8, 18, and 20) and keratins associated with basal cell compartments of squamous epithelia (keratins 5, 13, 14, and 17). We also tested 2 antibodies recognizing more than 1 keratin also directed against basal cell compartments of squamous epithelia (D5/16 B4 and 34betaE12). Bladder urothelium in PBS/IC showed distinct differences in the profiles of keratins 7, 8, 14, 17, 18, and 20 compared with literature reports for normal bladder urothelium. These were characterized by a shift from the normal bladder urothelial keratin phenotype to a more squamous keratin profile, despite the lack of morphologic evidence of squamous epithelial differentiation and a loss of compartmentalization of keratin expression. The severity of these changes varied between biopsy specimens. Whether these changes are primary or secondary to another underlying condition remains to be determined.     

Down-regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis

Sakamoto K, Aragaki T, Morita K‐i, Kawachi H, Kayamori K, Nakanishi S, Omura K, Miki Y, Okada N, Katsube K‐i, Takizawa T & Yamaguchi A
(2011) Histopathology 58, 531–542
Down‐regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis Aims: This study aimed to identify relevant keratin subtypes that may associate with the pathogenesis of oral epithelial neoplasms. Methods and results: Expression of all the keratin subtypes was examined by cDNA microarray analysis of 43 oral squamous cell carcinoma (OSCC) cases. Immunohistochemical expression of the major keratins was examined in 100 OSCC and oral epithelial dysplasia (OED) cases. Many changes in keratin expression were observed and, significantly, consistent down‐regulation of keratin 4 (K4) and K13 expression was observed. Aberrant expression of K4 and K13 was associated with morphological changes in the affected oral epithelium. Experiments with cell cultures transfected with various keratin subtypes suggested that alterations in keratin subtype expression can cause changes in cell shape and movement. Conclusions: Aberrant expression of K4 and K13, which are the dominant pair of differentiation‐related keratins in oral keratinocytes, indicates dysregulation of epithelial differentiation in OSCC and OED. These keratins, especially K4, may be useful for pathological diagnosis. We propose that the aberrant expression of K4 and K13 and concomitant up‐regulation of the other keratins may be one of the causative factors for morphological alterations in the affected epithelium.     

Are keratin proteins a better tumor marker than epithelial membrane antigen? A comparative immunohistochemical study of various paraffin-embedded neoplasms using monoclonal and polyclonal antibodies

Epithelial membrane antigen and keratin proteins represent markers of epithelial differentiation that may be detected in routine formalin-fixed, paraffin-embedded tissues. Eighty-seven neoplasms, including 48 adenocarcinomas of various types, squamous and transitional cell carcinomas, small-cell anaplastic carcinomas, carcinoid tumors, mesotheliomas, hepatomas, melanomas (metastatic), adrenal cortical carcinomas, germ cell tumors, and extramammary Paget's disease, were assessed to determine the relative effectiveness of these antigens as tumor markers. Immunoperoxidase studies were performed using monoclonal antibodies to epithelial membrane antigen and monoclonal (combined AE1 and AE3) and polyclonal (bovine muzzle keratins) antibodies to keratin proteins. In more than half the cases (50/87%), both markers yielded comparable results. However, in 29 cases (33%), keratin proteins were clearly superior to epithelial membrane antigen as a tumor cell marker. Particular discrepancies were apparent for some gastrointestinal adenocarcinomas, squamous cell carcinomas, hepatomas (hepatocellular type), spindle cell components of mesotheliomas, and carcinoid tumors. Epithelial membrane antigen represented a better marker in eight cases (9%), mainly for small-cell anaplastic carcinomas and some renal cell and pulmonary adenocarcinomas. Adrenal cortical carcinomas, melanomas, and seminomas were nonimmunoreactive for both antigens. Epithelial membrane antigen and keratin proteins represent useful complementary markers in diagnostic surgical pathology.     

Cytokeratin expression in non-neoplastic oesophageal epithelium and squamous cell carcinoma of the oesophagus

The expression of cytokeratins (CK) 19, 8, 18, 13, 10 and 7 was examined in 35 cases of squamous cell carcinomas of the oesophagus (10 well-differentiated, 13 moderately-differentiated, and 12 poorly-differentiated) and the adjacent mucosa by means of a panel of monoclonal antibodies on frozen sections. The study was undertaken to assess the pattern of expression of these keratins in oesophageal tumours and its relation to the degree of differentiation. The normal oesophageal epithelia expressed CK19 in 86%, CK18 in 17% and CK13 in 14% of cases. CK8, CK10 and CK7 immunoreactivity was not observed. The tumours expressed CK19 in 86%, CK8 in 46%, CK18 in 97%, CK13 in 83%, CK10 in 34% and CK7 in 29% of cases. Thus, the so-called simple epithelial markers CK18 and CK19 occurred in the majority of oesophageal squamous cell carcinomas. CK13 (the so-called non-keratinizing squamous epithelial marker) was only infrequently demonstrated in the non-neoplastic oesophageal mucosa, and its expression was more frequent in carcinomas. CK10 was not demonstrated in non-neoplastic mucosa, but was mostly associated with well-differentiated carcinomas. We therefore conclude that the pattern of expression of cytokeratins in oesophageal carcinomas is different from that in normal oesophageal epithelia and varies with differentiation.     

Keratins 8, 10, 13, and 17 are useful markers in the diagnosis of human cervix carcinomas

Several candidate tumor markers for cervical neoplasia have been identified. Among those are keratin markers, whose precise implications in the diagnosis are still under debate. In the present study, we aimed to clarify the usefulness of studying the expression of keratins 8, 10, 13, and 17 for diagnostic purposes in human cervix carcinomas. Forty-four invasive squamous carcinomas, 10 cervical intraepithelial neoplasia grade III (CIN III), and 10 reference cervix were examined immunohistochemically with monoclonal antibodies. Expression of keratins in reference exocervix, CIN III, and invasive carcinomas was as follows: keratin 8--0, 44.4%, and 57.1%, respectively; keratin 10-77.8%, 40%, and 19%, respectively; keratin 13--100%, 22.2%, and 25%, respectively; keratin 17-0, 40%, and 73.2%, respectively. In invasive carcinomas, expression of keratin 10 was significantly associated with keratinizing carcinomas. In conclusion, we observed that expression of keratins 8 and 17 and loss of keratins 10 and 13 are good markers of malignant transformation in human cervix. Keratin expression patterns, namely expression of keratin 10, can be useful for subtyping and grading squamous cell carcinomas of the cervix.     

Keratin filaments in epithelial cells of the excretory ducts of rabbit submandibular glands--an immunohistochemical and ultraimmunohistochemical study

To clarify the roles of various keratin proteins, the distributions of eight keratin intermediate filament proteins (keratins 7, 8, 10, 13, 14, 18, 19 and 20) in the epithelial cells of the excretory ducts of rabbit submandibular glands were studied immunohistochemically and ultraimmunohistochemically. The epithelia of excretory ducts were composed of columnar cells and basal cells. In the columnar cells, intermediate filaments formed a network at the apical area, that is, an apex network connected with desmosomes. Keratins 7, 18 and 20 were detected in the upper layer of the network and keratins 8, 18 and 20 in the lower layer. The intermediate filaments containing keratin 7 were also connected with hemidesmosomes on the basal side. Keratins 7, 18 and 20 were found throughout the entire cytoplasm of the columnar cells. Keratins 8 and 14 were expressed near the nucleus, forming a ring-like structure around the Golgi apparatus in the columnar cells. In the basal cells, by contrast, the intermediate filaments were concentrated around the nucleus, forming a juxtanuclear network which contained keratin 10. Keratin 13 was detected between the juxtanuclear network and the cell membrane, and was connected with both desmosomes and hemidesmosomes. Kratin 7 filaments were contained throughout the entire cytoplasm of the basal cells. These results suggested that different functional subsets of keratin filaments could be distinguished in the epithelial cells of the excretory ducts of the submandibular glands. In the columnar cells, keratins 7, 8, 18 and 20 play a role in cell-cell contact or cell-matrix contact, and both keratins 8 and 14 seem to be involved in the structure of the Golgi apparatus. In the basal cells, keratin 10 may serve to position and anchor the nucleus within the cell, and keratin 13 plays a role in cell-cell and cell-matrix contacts.     

Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis

 

Aims:

In this study the recently developed keratin 19 antibody RCK108 is biochemically and immunohistochemically characterized. Its applicability as a keratin marker in routinely processed histological tissue specimens is assessed.  

Methods and results:

The keratin 19 antibody RCK108 antibody was tested on normal and malignant routinely formalin-fixed, paraffin-embedded tissue specimens. It stains most, although not all, glandular epithelia and showed (focal) reactivity in the basal cell compartment of stratified epithelia. It was found to react with most epithelial tumours, including adenocarcinomas, squamous cell carcinomas and endocrine tumours of various origins.  

Conclusions:

Its reproducible and highly sensitive staining characteristics make RCK108 a useful antibody to be applied as a broad epithelial marker for carcinoma detection in routinely processed paraffin sections. As such, RCK108 is a specific reagent for practically all epithelial tumours. A few types of epithelial malignancies, known not to contain keratin 19, were negative for RCK108. Therefore the antibody is also useful in some narrow differential diagnostic considerations such as cholangiocellular carcinoma (RCK108 positive) vs. hepatocellular carcinoma (RCK108 negative). Another important feature of this antibody is that it shows very little reactivity in mesenchymal tissues, or mesenchymally derived tumours, as is frequently described for other keratin antibodies. A few leiomyosarcomas showed sporadic reactivity.     

Cytokeratins of normal epithelia and some neoplasms of the female genital tract

Cytokeratins are a family of polypeptides of intermediate filaments which in diverse epithelia are expressed in different, yet specific, combinations. We have studied the cytokeratins present in normal epithelia of the female genital tract, in comparison with those present in genital tract carcinomas, by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues and by immunofluorescence microscopy. Cells of ovarian mesothelium, oviduct, endometrium, and endocervix contain cytokeratin polypeptides nos. 7, 8, 18, and 19. By contrast, tonofilaments of the stratified squamous epithelia of vagina and exocervix contain cytokeratins 4, 5, 6, 13, 14, 15, 16, and 19. Exocervical regions distant from the endo-exocervical junction as well as vagina contain, in addition, the large (Mr 68,000) and basic cytokeratin component no. 1, previously described in epidermis. Endocervical squamous metaplasia at the endo-exocervical border displays a complex cytokeratin pattern, probably due to cell-type heterogeneity. Similar cytokeratin patterns are also observed in genital tract epithelia of the cow and mouse. In human carcinomas of the female genital tract, two main types of cytokeratin patterns can be distinguished. Ovarian carcinomas and endometrial adenocarcinomas express cytokeratins 7, 8, 18, and 19 and, thus, maintain the pattern of the cells of their origin. In endocervical adenocarcinomas the additional presence of component no. 17 has been noted. Nonkeratinizing squamous cell carcinomas of the cervix show a very complex pattern (cytokeratins 5, 6, 7, 8, 13, 14, 15, 17, 18, and 19). Keratinizing squamous cell carcinomas of the cervix display lower complexity and lack cytokeratins 7, 8, and 18. When frozen sections are examined by immunofluorescence microscopy, all epithelia of the genital tract are stained with the monoclonal cytokeratin antibody KG 8.13. Simple epithelia but not the stratified epithelia of vagina and exocervix also react with monoclonal antibodies specific for cytokeratins 8 or 18. The value of cytokeratin polypeptide patterns in distinguishing diverse epithelial cell types of the female genital tract, in elucidating the histogenesis of neoplasms, and in providing a new tool for the differential diagnosis of tumors is discussed.     

Epithelial cell markers and proliferating cells in odontogenic jaw cysts

The expression of keratins, CEA, EMA, and rat liver antigen (RLA) and the presence of Ki67+ proliferating cells were studied in the epithelial linings of 50 odontogenic cysts using an indirect immunoperoxidase method on acetone-fixed frozen sections. All cysts were positive with monoclonal antibodies of broad keratin specificity (CK1, AE1-3), and between 40 and 100 per cent of epithelial cells expressed keratins 13 and 19. Keratins 7, 8, and 18 were rarely expressed although surface cells in areas of mucous metaplasia often expressed keratins 7 and 18. Expression of keratin 10/11 was related to the presence of a well-ordered epithelial lining and was detected in isolated cells in 4/32 non-keratinizing cysts and in the upper suprabasal cell layers of 17/18 keratocysts. Although CEA, EMA, and RLA were detected in the epithelium of all specimens, the pattern of expression of CEA and EMA differed between cyst types. Ki67+ proliferating cells were most prevalent in keratocyst epithelia, where they were usually found within lower suprabasal layers which were negative or weakly positive for keratins 10/11 and 13. These results indicate differences in keratin, CEA, and EMA expression between cyst types which appear to be dependent on epithelial differentiation/structure rather than cyst type or histogenesis. Although these differences may not be of diagnostic significance, the consistent expression of both keratins 13 and 19 may provide a useful marker of odontogenic epithelium in general.     

Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia.

The expression of keratins in normal cervical epithelia, metaplastic epithelium, and cervical intraepithelial neoplasia (CIN) grades I, II, and III is investigated with a panel of keratin polypeptide-specific monoclonal antibodies. This approach allowed the detection of individual keratins 4, 7, 8, 10, 13, 14, 18, and 19 at the single-cell level. By using an antibody recognizing keratins 5 and 8 (RCK 102) and two antibodies specific for keratin 8 (CAM 5.2 and M 20), it was also possible to derive information on the distribution of keratin 5. Our results show that during immature squamous metaplasia there is an acquisition of keratins typical of squamous epithelium, ie, keratins 4, 5, 13, and 14. This process continues during further differentiation to mature squamous metaplasia. In premalignant lesions the expression pattern of the progenitor reserve cells and immature squamous metaplastic epithelium is partly conserved. However, in most cases an induction in the expression of the keratins 4, 13, and 14 was observed. Furthermore, CIN III shows a more extensive expression of keratins typical of simple epithelia, ie, keratins 8 and 18, as compared to CIN I and CIN II.     

Keratin expression in anal carcinoma: an immunohistochemical study

The keratin expression of 40 frozen tissue specimens of anal carcinoma was investigated using a panel of 17 monoclonal antibodies to 14 individual keratins. The tumours were divided into three histological subgroups showing pure squamous, squamous and basaloid, or squamous and glandular differentiation. A further assessment of the tumour grade was made. The overall profile was of expression of keratins 4, 13, 17, 18 and 19 across the majority of the tumours, with the minority expressing keratins 1 and 10, and keratin 7. Dedifferentiation was associated with loss of expression of keratinocyte keratins, particularly the cornification markers keratin 1 and 10, and K6 and 16 associated with keratinocyte hyperproliferation and differentiation. This correlated with acquisition of the simple epithelial keratins 7 and 8. Compared with the tumours as a whole, well differentiated squamous tumours (the most easily identifiable histological group) showed consistent positivity for keratins 6 and 16, expressed suprabasally, while simple keratins 18 and 19 were also found. Independent of grade, mixed tumours showed more widespread positivity for simple epithelial keratins 7, 8 and 18 and loss of expression of cornification keratins 1 and 10 and K6 and 16 compared with pure squamous tumours. The relatively limited keratin profile of pure squamous tumours, predominantly consisting of keratinocyte keratins, suggests that these malignancies are less likely to originate from the region of the anal canal where the keratin profile is heterogeneous, i.e. the anal transitional zone.     

Patterns of keratin polypeptides in 110 biphasic, monophasic, and poorly differentiated synovial sarcomas

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor. Received: 17 February 2000 / Accepted: 3 April 2000     

The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors

Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.     

Keratin 17 expression as a marker for epithelial transformation in viral warts.

The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors.