Cytokeratins and lung carcinomas

BACKGROUND: Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival. RESULTS: CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.     

Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas.

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and cytopathology, in which they add to a more refined diagnosis of (adeno)carcinomas.     

Cytokeratin typing as an aid in the differential diagnosis of primary versus metastatic lung carcinomas, and comparison with normal lung

Due to more efficient chemotherapy protocols, the number of second and even third primary carcinomas is steadily increasing. To denominate the possible origin of a carcinoma, different markers are available as an aid, e.g. hormones, proteins and lipoproteins, secretion products and cytoskeletal proteins. Cytokeratins (CKs) have gained new popularity; however, they have not been extensively evaluated in lung tumours. In our study we evaluated the staining patterns of CK polypeptides 4-8, 10, 13, 14, and 17-20 and high molecular weight (HMW) CK polypeptides in routinely processed primary lung carcinomas and lung metastases of diverse origin. As expected, immunohistochemical investigation gave no clear-cut results, but, with statistical analysis, lung adenocarcinomas could be separated from metastatic adenocarcinomas using CK 5 and 18 and HMW CK (specificity 92.5%, sensitivity 62.5%). The different origin of the metastases could often be detected using CK 18 and CK 20. Lung clear cell carcinomas and large cell carcinomas with clear cell areas could be distinguished from metastatic renal clear cell carcinomas by the CK 7 staining reaction. Squamous cell carcinomas of the lung and metastatic squamous cell carcinomas of the larynx, pharynx and oesophagus could not reliably be separated in part due to the few number of cases available. CK polypeptide typing is thus an additional aid in the differential diagnosis of lung carcinomas versus carcinomas metastatic to the lung.     

Immunohistochemical distinction of human carcinomas by cytokeratin typing with monoclonal antibodies.

Carcinomas of different origin have been tested in immunofluorescence microscopy with the monoclonal murine antibodies CK1-CK4, which recognize a single cytokeratin polypeptide (human cytokeratin No. 18) present in simple but not in stratified squamous epithelia, and with the monoclonal antibody KG8.13 and guinea pig kerA antibodies, both of which recognize a variety of cytokeratins common to almost all epithelial cell types. Tumors derived from simple epithelia, including adenocarcinomas and some other tumors such as ductal breast carcinomas, were strongly stained by all three antibodies. So was a transitional carcinoma of the bladder. In contrast, basal cell epithelioma, cloacogenic carcinoma, and squamous cell carcinoma of skin, tongue, and esophagus appeared negative with CK1-CK4 but positive with the other two antibodies. Other squamous cell carcinomas derived from epiglottis and cervix uteri showed a mixture of positive and negative cells when tested with CK1-CK4, although all tumor cells were positive when tested with KG8.13 and with kerA. Thus, use of an appropriate collection of cytokeratin antibodies with different specificities not only allows tumors of epithelial origin to be distinguished from other tumor types but, in addition, allows a further subdivision of carcinomas in relation to their histologic origin.     

Expression of epithelial and neural antigens in small cell and non small cell lung carcinoma

Seventy-one lung carcinomas from 66 different patients were stained with a panel of monoclonal antibodies. Twenty-nine were small cell lung carcinoma (SCLC), 15 adenocarcinomas, 17 squamous carcinomas and 10 large cell carcinomas. Three of the monoclonal antibodies recognize different cytokeratins, three recognize other epithelial antigens and one recognizes a neural antigen. Both formalin-fixed and cryopreserved tumours were studied using an indirect immunoperoxidase method. 23/29 SCLC reacted with all but one of the antibodies which recognize epithelial antigens. This staining was similar to that seen in non small cell lung carcinomas (NSCLC) and provides further evidence that SCLC are true epithelial tumours. All but one of the SCLC stained with the antibody recognizing a neural antigen. This antibody did not stain squamous or adenocarcinomas. However, four of the large cell carcinomas stained well with this antibody, suggesting that SCLC and some large cell carcinomas share a common pathway of differentiation. There were variations of staining seen both within and between tumours. This has obvious implications if immunotargetting with monoclonal antibodies is to be used diagnostically or therapeutically.     

Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinomas and follicular thyroid adenoma

Keratin expression with the use of chain-specific monoclonal antikeratin antibodies was investigated in normal thyroid tissue (n = 4), colloid nodules (n = 19), follicular thyroid adenomas (n = 18), follicular carcinomas (n = 10), and papillary carcinomas (n = 12). Frozen sections were stained with monoclonal antibodies M20 (keratin 8), M9 (keratin 18), and LP2K (keratin 19) with the use of the indirect immunoperoxidase technique. The immunohistochemical findings showed that the expression of keratins 8 and 18 was equally extensive in all normal, benign, and malignant lesions tested. In contrast, different staining patterns were observed with the use of monoclonal antibody to keratin 19. Follicular carcinomas were only focally stained with this antibody or were not reactive at all. Keratin 19, however, was present in all the tumor cells of papillary tissues and in a moderate amount of cells of nonneoplastic thyroid lesions and follicular adenomas. In papillary carcinoma, an identical homogeneous expression of keratin 19 was observed in both papillary and follicular structures, which suggests a common cellular origin. These results show that immunohistochemical staining with the use of monoclonal antibody against keratin 19 is useful to distinguish papillary thyroid carcinomas from follicular adenomas and follicular thyroid carcinomas.     

A 22-kd surface antigen detected by monoclonal antibody E 48 is exclusively expressed in stratified squamous and transitional epithelia.

After immunization of mice with viable cells of a metastasis of a laryngeal squamous cell carcinoma, a monoclonal antibody E 48 was obtained that detects an epitope present exclusively in squamous and transitional epithelium and their neoplastic counterparts. Immunoblotting revealed that E 48 recognizes a 22 kd molecule. Seventy-five of 76 squamous cell carcinomas from the head and neck, lung, cervix, and skin stained positively, whereas various adenocarcinomas from the colon, lung, and breast, and small cell lung carcinomas consistently stained negatively. The E 48 antigen, which is formaldehyde resistant, appears to be a reliable marker for differentiation of squamous cell carcinomas from adenocarcinoma, and small cell carcinomas.     

Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.     

Differential diagnosis of gastrointestinal carcinomas by using monoclonal antibodies specific for individual keratin polypeptides

Monoclonal antibodies which recognize particular keratin polypeptides have been used to analyze normal human tissues including pancreas, stomach, colon, gall bladder, and liver as well as tumors of the gastrointestinal tract by immunohistological techniques. Broad specificity (lu5), ker 8 (Troma 1) and ker 18 (CK2) antibodies were positive while a ker 14 specific antibody (CKB1) was negative on all specimens tested. Differential staining patterns were seen with a ker 7 (CK7) and a ker 19 (KA4) antibody. Both antibodies stained gall bladder epithelium, pancreatic ducts but not acinar cells, as well as pancreatic ductal adenocarcinomas. KA4 but not the CK7 antibody stained adenocarcinomas of the stomach and large bowel. Both antibodies stained bile ducts and cholangiocellular carcinoma of the liver but did not stain hepatocytes or hepatocellular carcinomas. The results with keratin monoclonal antibodies compare well with those obtained by others using two dimensional gel electrophoresis and they further support the idea that monoclonal antibodies specific for particular keratin polypeptides will find applications in routine pathological diagnosis.     

Are epidermal growth factor and transforming growth factor responsible for pseudoepitheliomatous hyperplasia associated with granular cell tumors?

Granular cell tumors (GCT) are uncommon benign neoplasms that have a predilection for the head and neck region. These tumors can frequently be associated with pseudoepitheliomatous hyperplasia (PEH), which in turn may be mistaken for squamous cell carcinoma. Although epidermal growth factors are overexpressed in squamous cell carcinomas of the head and neck, their presence in PEH, especially its relation to GCT, is unknown. We hypothesize that the expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in GCT have a role in the development of PEH overlying some GCT. Sections from 13 cases of GCT (five with overlying PEH) were examined histologically and evaluated immunohistochemically using monoclonal antibodies for EGFR, EGF, and TGFalpha. These were compared with nine cases of PEH independent of GCT. Two of five GCT with overlying PEH and two of six GCT without overlying PEH stained positively for TGFalpha. None of the GCT stained with EGFR or EGF. All cases of PEH, whether or not associated with GCT, were reactive for EGFR and EGF. Four of the five cases of PEH overlying GCT stained with TGFalpha. The staining pattern and intensity of all three antibodies were comparable to that of the adjacent normal squamous mucosa. Among the three antibodies, only TGFalpha in GCT appears to be related to the development of PEH. Epidermal growth factor receptor and EGF do not seem to be directly involved. The reason of PEH formation associated with GCT in the absence of growth factors is unknown.     

Discrimination of cell types in primary transitional cell carcinoma by monoclonal anti-cytokeratin antibodies.

The morphologic discrimination between low and high grade malignant tumor cells arising in the urinary bladder is a major diagnostic problem in cytopathology. Using immunochemical peroxidase staining of cytokeratins (CKs) of human bladder exfoliative cytology specimens, we have been able to discriminate between transitional cell carcinoma cells, atypical cells and normal bladder cells. Commercially available monoclonal antibodies used in this study were: anti-CK 13 (Sigma K8.12), anti-CK 5, 7 and 8 (Sigma K8.13), anti-CK 19 (Sigma K4.62), and anti-CK 18 (Transformation Res. 1091). When normal bladder cells are stained with these antibodies, CK 18 is specific for superficial cells; CK 13 is specific for the basal type cells and CKs 5, 7, 8 and 19 are expressed by all urothelial cell types. Four cases diagnosed by cytopathological criteria as 'atypical' and 7 diagnosed as 'positive' (various grades) were used in this study. Cytologic diagnosis was confirmed by histopathology in 7 cases. Tissue was not available for histopathology in 4 cases. Malignant cells with a 'basal' or 'immature' phenotype preferentially stained with CK 13 and were associated with increased metastatic or malignant potential. Patients with higher grade tumors had more cells positive for CK 13 than did patients with atypical or lower grade malignancies. Patients with well-differentiated, low grade tumors predominantly shed cells that expressed CK 18 and CK 19. High grade, invasive bladder lesions were characterized by many cells expressing CK 13, and fewer cells expressing CK 19. The combination of diagnosis by morphologic criteria on Papanicolaou-stained specimens with immunochemical characterization of the same cells for CKs facilitate an accurate diagnosis of bladder lesions.     

Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours

The expression of cytokeratins (CK) 1, 4, 5/6, 8, 13, 18, 19 and 20 and involucrin in 42 cases of squamous cell carcinomas from various locations was examined. The tumours expressed CK5/6 in 55%, CK8 in 76%, CK13 in 43% and CK19 in 95% of cases. The CK5/6-positive primary tumours were from uterine cervix, head and neck, lung, skin, oesophagus is and urinary bladder, and the CK13-positive primary tumours were from uterine cervix, lung and vulva. Metastatic squamous cell carcinomas from head and neck more frequently expressed CK5/6 and 13, 7/7 (100%) and 6/7 (86%) compared with 3/5 (60%) and 0/5 (0%) in the primary squamous cell carcinomas. Few cases were CK1, CK4 and CK18 immunoreactive, CK20 immunoreactivity was not observed. Involucrin was expressed in 71% of tumours, and most of the involucrin-positive cells were located at the central parts of tumour cell clusters except for one case in which the peripheral cells around tumour cell clusters were positive. Thus, expression of the so-called simple epithelial markers CK8 and CK19 occurs in the majority of squamous cell carcinomas. The absence of CK20 immunoreactivity may be helpful in differential diagnosis.     

Keratins versus epithelial membrane antigen in tumor diagnosis: an immunohistochemical comparison of five monoclonal antibodies

Among the monoclonal antibodies capable of detecting epithelial lineage, some recognize keratin and others identify antigens of epithelial membranes. Of the latter, the most commonly used is directed against an antigen present in cell membranes derived from milk fat globules, epithelial membrane antigen (EMA). To determine their relative sensitivity and specificity and hence their diagnostic value, we compared four commercially available monoclonal antibodies to low-molecular-weight keratins--AE1, CAM 5.2, PKK1, and 35 beta H11--with the monoclonal antibody to EMA (anti-EMA). We studied 383 samples of human neoplasms of diverse histogenetic types and degrees of differentiation. Anti-EMA was found to be less sensitive than the monoclonal antibodies to keratin in several epithelial tumors, including tumors of the prostate (11 of 13 negative), gastrointestinal tract (13 of 34 negative), and thymus (seven of eight negative). Anti-EMA was also less sensitive in mesotheliomas (nine of 24 negative). Of the embryonal carcinomas, all stained with the monoclonal antibodies to keratin, whereas none stained with anti-EMA. False-positive staining with anti-EMA was seen in two of 14 T-cell lymphomas. We conclude that the monoclonal antibodies to low-molecular-weight keratins are more sensitive and specific for the identification of epithelial origin of neoplasms than is monoclonal anti-EMA. Anti-EMA should not be used as the sole marker of epithelial differentiation in tumor diagnosis.     

Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections

CD56 is immunohistochemically detectable in virtually all small cell carcinomas on frozen sections. The authors retrospectively tested the usefulness of the monoclonal antibody 123C3 against CD56 to differentiate pulmonary and extrapulmonary small cell carcinomas from nonneuroendocrine non—small cell carcinomas by paraffin-section immunohistochemistry after antigen retrieval. The study included 70 small cell carcinomas and 344 primary and metastatic nonneuroendocrine carcinomas of various primary sites. The staining results were compared with specific neuroendocrine markers (CD57, Chromogranin A, Synaptophysin). The monoclonal antibody 123C3 diffusely stained most small cell carcinomas with a strong membranous pattern (sensitivity: 0.99). The staining intensity was not diminished in areas with crush artifacts or after decalcification. The neuroendocrine markers had a combined sensitivity of only 0. 44 for small cell carcinomas. With regard to nonneuroendocrine carcinomas, the 123C3 antibody stained 7 of 28 ovarian carcinomas, 6 of 30 renal cell carcinomas, 2 of 10 endometrial carcinomas, two of three nonneuroendocrine large cell carcinomas of the lung, 1 of 38 adenocarcinomas, and 4 of 52 squamous cell carcinomas of the lung. Urothelial carcinomas, hepatocellular carcinomas, squamous carcinomas of the head/neck and cervix uteri, as well as adenocarcinomas of the breast, stomach, colon, pancreas, and prostate, showed no immunoreactivity for CD56. The specificities of 123C3 and the combined neuroendocrine markers for small cell carcinomas were 0. 94 and 0. 95, respectively. The authors conclude that monoclonal antibody 123C3 might be useful for the immunohistochemical differentiation of small cell carcinomas from nonneuroendocrine carcinomas on paraffin sections, especially in small and crushed biopsy specimens.     

Immunohistochemistry of the cytoskeleton of human prostatic epithelium. Evidence for disturbed organization in neoplasia.

An indirect immunoperoxidase technique was used to evaluate keratin, actin, tubulin, and calmodulin immunoreactivity in histologic sections of normal, hyperplastic, and neoplastic human prostate. Polyclonal as well as monoclonal keratin antibodies produced equivalent and intense staining of normal epithelium. The immunoreactivity of normal prostate with keratin antibodies was more pronounced than with antibodies to the other components of the cytoskeleton. Variation in staining for components of the cytoskeleton was minimal. The same findings applied to hyperplastic prostate. The immunoreactivity of prostate tumors with antibodies to these cytoskeletal proteins differed markedly from normal prostate. Prostatic carcinomas showed reduced keratin immunoreactivity with a panepithelial antibody, but unaltered or enhanced immunoreactivity with tubulin, actin, and calmodulin antibodies. Many tumors were unreactive with a monoclonal keratin antibody that was strongly reactive with tissues that contained cytokeratin 18 (45-kd) and which intensely stained normal and hyperplastic prostate. In addition, prostate carcinomas often yielded heterogeneous patterns of staining with actin, tubulin, and calmodulin antibodies in contrast to normal and hyperplastic prostate, which showed uniform staining. The results suggest that a disturbance in the organization of the cytoskeleton may accompany neoplastic transformation of human prostate.     

Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases.

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.     

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.     

The limited difference between keratin patterns of squamous cell carcinomas and adenocarcinomas is explicable by both cell lineage and state of differentiation of tumour cells.

AIM: To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma. METHODS: Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised. RESULTS: The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied. CONCLUSIONS: There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.