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The significance of limited resections, including wedge resection and segmentectomy, remains controversial because of their curability rates. In the current study, the objective was to determine a strategy for the treatment of patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) based on the pathologic findings from 184 patients with ROSCC who underwent resection.In Miyagi Prefecture, 1422 patients with lung carcinoma were diagnosed during a mass screening program between 1982 and 1995. Among them, 236 patients had ROSCC, and 184 patients with ROSCC underwent pulmonary resection followed by systemic lymph node dissection.Pathologically, only 0.9% of the ROSCCs that were within the range of endoscopic visibility were revealed to have lymph node involvement, whereas 13% of patients with extracartilage invasion had lymph node involvement. Early ROSCC, which means ROSCC that is limited within the cartilaginous layer and is without lymph node involvement, comprised 90% of ROSCCs that measured10 mm in longitudinal extension, comprised 77% of ROSCCs that measured 10-29 mm in longitudinal extension, and comprised 33% of ROSCCs that measured30 mm in longitudinal extension. Eighty-nine percent of the tumors with lymph node involvement had extracartilaginous invasion. The 3-year survival rate of patients after undergoing photodynamic therapy was 100% when their tumor was regarded as early ROSCC (i.e., within 10 mm in longitudinal extension and within the range of endoscopic visibility). To date, 18 patients with ROSCC underwent segmentectomy, and all of these patients are alive without tumor recurrence. The incidence rate of multiple lung carcinomas, including synchronous and metachronous tumors, in patients with ROSCC was 22%.The authors concluded the following: 1) Patients with lesions that are within the range of endoscopic visibility and that measure10 mm in longitudinal extension are candidates for photodynamic therapy. 2) Patients with lesions that are beyond the range of endoscopic visibility or that measure10 mm in longitudinal extension are candidates for segmentectomy as long as intraoperative examination shows a tumor free bronchial stump and negative lymph nodes 11-13. 3) Patients with lesions that show bronchial obstruction or extrabronchial invasion should undergo standard resection.

BACKGROUND Bronchial epithelial cells produce a significant amount of granulocyte-macrophage-colony stimulating factor (GM-CSF), which is believed to mediate both the host defense and inflammation. Recently, GM-CSF has been demonstrated to be produced by several tumor cells and also to be associated with tumor growth and metastasis. In the current study, the authors investigated the biologic role of GM-CSF produced by squamous cell lung carcinoma. METHODS The production of GM-CSF from 17 human lung carcinoma cell lines was determined by an enzyme-linked immunoabsorbent assay. In vitro invasiveness was investigated by using a Biocoat Matrigel (Collaborative Biomedical Products, Bedford, MA) precoated invasion chamber. The activity of the matrix metalloproteinases (MMPs) were examined by gelatin zymography. The expression of GM-CSF in 113 cases of resected nonsmall cell lung carcinoma was analyzed immunohistochemically, and the association between the expression of GM-CSF and clinicopathologic features was investigated. RESULTS The production of GM-CSF by squamous cell carcinoma cell lines was closely related to the in vitro invasiveness and MMP activity of the cancer cells. Recombinant GM-CSF stimulated the invasiveness of less invasive LK-2 and LC-1 cells in a dose-dependent manner, and this stimulation was abrogated by the neutralizing anti-GM-CSF antibody. Furthermore, anti-GM-CSF antibody decreased the invasiveness of highly invasive EBC-1 and NCI-H157 cells. GM-CSF also increased the MMP activity of LK-2 and LC-1 cells. Of 113 resected nonsmall cell lung carcinomas, 30 of 71 squamous cell carcinomas (42.3%), and 24 of 42 adenocarcinomas (57.1%) stained positively for GM-CSF. The expression of GM-CSF in squamous cell carcinomas was associated with the local invasion by the primary tumor. CONCLUSIONS These results suggest that the production of GM-CSF is involved in both the in vitro invasiveness and the local progression of squamous cell carcinoma of the lung. Cancer 1998;82:2173-2183. © 1998 American Cancer Society.

Background. The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. Methods. Using a projection microscope and a simple test system in fields of vision systematically selected from the whole tumor area of one routine section, five quantitative histopathologic variables were estimated: the mean nuclear volume, the mean nuclear profile area, the density of nuclear profiles, the volume fraction of nuclei to tissue, and the number of mitotic profiles per 103 nuclear profiles. For each patient, information was recorded regarding sex, age at diagnosis, and clinical stage of disease. Results. Single-factor analyses showed that a favorable prognosis was associated with early clinical stages (Stages I and II) and young age (P ≦ 0.03), and that females tended to do better than males (P = 0.09). Estimates of the mean nuclear volume were of prognostic significance (P = 0.02), small nuclei being associated with the worst prognosis. In a multivariate Cox analysis, clinical stage, age, and mean nuclear volume were found to be parameters of significant, independent prognostic value. Conclusions. The present feasibility study indicates that estimates of the mean nuclear volume are of prognostic value, independent of the clinical stage of disease. This quantitative histopathologic variable is highly reproducible and easily obtained using an unbiased stereologic method. Thus, the mean nuclear volume may be a parameter of future importance in the clinical management of patients with carcinoma of the lung.

Background. Squamous cell lung carcinoma (SLC), the most frequent type of lung cancer, generally is treated surgically and its prognosis is poor. The only current clinically useful prognostic criterion is lymph node staging (TNM classification). Expression of a novel tumor-associated carbohydrate epitope Galβ1–3[Fucαl-4]GlcNAcβ1-4[Fucα1–3]GlcNAcβ1–3Galsl-4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the growth pattern of SLC cell lines in athymic mice and in vitro. This implies that the 43-9F epitope may be related to tumor progression in patients with SLC and that, as such, it could be of prognostic value. Methods. Primary tumor specimens from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10 with small cell carcinoma, 16 with large cell carcinoma, and 11 with adenosquamous carcinoma) were examined by immunohistochemical studies on formalin-fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the 43-9F antigen. Univariate and step-wise Cox regression analyses were used to compare survival time by histopathologic diagnosis, smoker status, TNM classification, and type of surgical treatment. Results and Conclusions. Patients with 43–91: epitope-positive SLC tumors had a significantly (P < 0.01) better prognosis than patients with epitope-negative tumors. In contrast, no association was seen between 43-9F epitope expression and survival time for patients with lung adenocarcinomas. Further, the prognostic value of 43-9F expression in SLC was found to be superior to the N-classification with the added advantage that it requires access only to primary tumor tissue and thus is available before therapy. Cancer 1992; 70:1867–1872.

To assess the prognostic value of DNA ploidy in non-small cell lung cancer (NSCLC), we performed a flow cytometric study using paraffin-embedded archival material from 158 patients who underwent surgical resection between 1980 and 1982. Single-variable histograms were examined and the results of these histograms were correlated with clinicopathologic characteristics and outcome. Histograms that could be analyzed were obtained in 146 cases, of which 85 (58%) were aneuploid and 61 (42%) were diploid. Survival analysis showed that patients with diploid squamous cell carcinomas (SCC) survived significantly longer than those with aneuploid SCC (a 5-year survival rate of 70% as compared with 26% [P = 0.002], respectively), and the results were independent of stage. However, DNA ploidy was not a significant prognostic factor in non-SCC (P = 0.337). Ploidy did not correlate with other clinicopathologic variables such as stage, nodal status, degree of differentiation, nuclear grade, and mitotic rate. These results suggest that DNA ploidy, as determined by flow cytometric analysis, provides an independent prognostic variable for patients with SCC and that it should be considered in treatment planning. However, non-SCC of lung may have different biologic variables, and their prognostic variables should be evaluated separately.

BACKGROUND Recently, the authors reported identification and cloning of several novel immunogenic antigens in squamous cell lung carcinoma. Of 14 corresponding genes, 9 mapped in an amplified chromosomal region with the gene for eIF-4G that was amplified most frequently. METHODS Recombinant eIF-4G was expressed in E. coli and screened with sera from patients with squamous cell carcinoma of the lung and of the head and neck. Protein extracts from squamous cell carcinoma tissues were analyzed for eIF-4G expression by Western blot analysis. Mutation analysis was performed using an automatic DNA sequencer. RESULTS The authors screened a spectrum of 33 heterologous sera from lung carcinoma patients and detected antibodies against eIF-4G in 5 of these sera (15%). They found no immune response to eIF-4G in 17 sera from squamous cell carcinoma tissues derived from the head and neck. In addition, no antibodies were found to eIF-4G in a group of 17 control sera from individuals without known tumor formation. Sequence analysis of the eIF-4G gave no indication of mutations. To analyze the expression of eIF-4G, a monoclonal antibody was used. Western blot analysis clearly showed overexpression in the tumor tissue compared with the corresponding normal lung tissues. CONCLUSIONS The translation initiation factor eIF-4G is the first protein in which the gene shows amplification, has increased expression in a human tumor, and induces an immune response in patients. eIF-4G lends itself as a marker for the diagnosis of and possibly as a future therapeutic target in patients with squamous cell lung carcinoma. Cancer 2001;92:822–9. © 2001 American Cancer Society.

BACKGROUND Telomerase activation is believed to be play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS The mean values (± the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 ± 7.5, 13.9 ± 14.8, 18.5 ± 20.8, and 54.5 ± 22.3 U/μg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/μg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/μg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 ± 840, 1936 ± 1704, 3019 ± 2607, and 12965 ± 18008 copies/μg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages. Cancer 2001;92:849–55. © 2001 American Cancer Society.

The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot.

BACKGROUND Immunoreactivity for chromogranin A (Cg A) is associated with the presence of neurosecretory granules in tumor cells, but immunohistochemical staining for Cg A may be absent in small cell lung carcinoma (SCLC), which has only a few secretory granules. Localization of Cg A mRNA is a useful indicator of the site of synthesis of a particular protein and possibly the rate of synthesis, and it is not dependent on posttranslation events within the cells. However, it is difficult to detect the low levels of mRNA copies using the standard non-radioisotope (RI) oligonucleotide probe. METHODS The authors analyzed Cg A mRNA in 20 cases of SCLC in formalin fixed, paraffin embedded tissue using a new, highly sensitive in situ hybridization method that was developed from the maximized immunohistochemistry (ImmunoMax) method. They also investigated Cg A mRNA in nonsmall cell lung carcinoma (NSCLC), including ten cases each of adenocarcinoma and squamous cell carcinoma of the lung. RESULTS All examined SCLC tissues showed a positive reaction for Cg mRNA. No NSCLC specimens showed any positive reaction for Cg A mRNA. CONCLUSIONS The detection of Cg A mRNA using the new, highly sensitive in situ hybridization method with a non-RI oligonucleotide probe can be used to characterize neuroendocrine differentiation of lung tumors even when the Cg A protein is not detected by immunohistochemistry. The authors believe this is a first step toward better diagnosis and treatment for patients with SCLC. Cancer 1998;82:468-73. © 1998 American Cancer Society.

The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus in not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously.

We have evaluated 3,620 bone marrow aspirates from 2,877 patients with solid tumors for the presence of clinically unsuspected metastasis. All aspirates were obtained from the iliac crest as part of the prechemotherapy workup and processed as smear and paraffin sections of the clot. Of the 2,877 patients, 263 (9.1%) showed metastatic tumor. Of these, metastasis was most frequent in neuroblastoma (48.2%), Ewing's sarcoma (35.5%), oat cell carcinoma (20.7%), prostate carcinoma (20.3%), breast carcinoma (19.6%), squamous cell carcinoma of the lung (15.7%), rhabdomyosarcoma (16.2%), and melanoma (6.8%). In most instances (92%), tumor cells were demonstrated simultaneously on both smears and clot sections. However, in lung and breast carcinoma, metastasis was noted more frequently in clot sections, while smears were superior for detecting both neuroblastoma and rhabdomyosarcoma. The prognostic significance of bone marrow involvement in 83 patients with state IV malignant melanoma scheduled for immunochemotherapy was investigated. In 39 patients (Group B, no bone marrow infiltration), the median survival was 59 weeks. In 44 patients (Group A, infiltrated bone marrow), the median survival was 6 weeks. Although bone marrow metastasis did not preclude response to immunochemotherapy, after 40 weeks only two patients of Group A were still alive, compared to 16 in Group B. This study demonstrates the usefulness of combining clot section and smear examinations for increased detection of unsuspected bone marrow metastasis and suggests the prognostic significance of bone marrow involvement in malignant melanoma.

This is a report of a gastric perforation secondary to a metastasis from a primary squamous cell carcinoma of the lung in a 70-year-old white man who was being treated with cimetidine for a presumed benign gastric ulcer. The literature concerning bronchogenic carcinoma metastasizing to the stomach and small bowel is reviewed, and the effect of cimetdine on malignant gastric ulcers is discussed.

Two patients with Stage I (T1-2N0M0) squamous cell bronchogenic carcinoma, diagnosed and staged at thoracotomy, survived five years and eight years, respectively, before the development of small cell, oat cell anaplastic lung cancer. Both patients are alive and clinically stable on combination chemotherapy five and 14 months, respectively, after diagnosis of small cell lung cancer.

A randomized prospective study was conducted comparing vindesine (VDS) with doxorubicin and cyclophosphamide (D/C) in the treatment of advanced squamous cell carcinoma of the lung. No patient had a complete response. Seven of 28 (25%) patients had partial response (PR) to VDS while one of 19 (5%) had a PR to D/C (P less than 0.08). Adding PR plus minor response (MR), ten of 28 (36%) patients responded to VDS while two of 19 (11%) responded to D/C (P less than 0.05). Median survival was improved among patients showing PR and MR over those not responding (P less than 0.05). This study concludes, VDS is an active agent in the treatment of squamous cell carcinoma of the lung and should be considered for combination chemotherapy and adjuvant trials. VDS toxicity appears acceptable with six weekly doses of 3 mg/m2. The benefit of a maintenance schedule could not be demonstrated.

The interaction between the antibiotic bleomycin and x-radiation has been studied in vitro and in vivo. Tissue culture results appear to reflect in vivo sensitivities correctly. Simultaneous exposure to bleomycin and gamma radiation enhances killing of both sensitive and resistant lines. Data from a pilot study combining bleomycin with conventional radiation for unresectable squamous cell carcinoma of the lung suggest that the simultaneous administration of bleomycin (10 mg/m2 intravenously twice weekly) with short-course radiation treatment is well tolerated and without dangerous pulmonary complications. Tumor response was greater in the combined-therapy group (46%) than in radiation-only controls (26%); median survivals were 13 and 6 months, respectively. Unlike previously published data, responders appeared to have a significant survival advantage over nonresponders, suggesting that bleomycin may be slightly effective in inhibiting the development of systemic metastasis, and that it positively enhanced local control of primary disease.

Atrial natriuretic factor is a new peptide hormone synthesized in the heart which has potent natriuretic, diuretic, and vasodilatory properties. A 47-year-old man with squamous cell carcinoma of the lung resected 6 months previously presented with syncope secondary to hypotension and a low serum sodium. He was evaluated to determine if atrial natriuretic factor (ANF) might be the etiology of this clinical picture. His plasma concentration of atrial natriuretic factor was increased three-fold over that of 70 normotensive person. Further evaluation revealed metastatic lesions in the right and left cardiac atria with the mass on the left occluding 75% of the left atrial chamber. The mass effect in the atria increasing atrial stretch and atrial pressure one would expect was the main contributor to the increased ANF level. The contribution of direct tumor invasion into the atria and/or production of atrial natriuretic factor by the tumor itself to produce this elevated plasma level of atrial natriuretic factor could not be determined, but this markedly elevated level of atrial natriuretic factor does appear to be the etiology of this patient's clinical picture.

The accuracy of chest computerized tomography (CT) in detecting malignant hilar and mediastinal involvement by squamous cell carcinoma of the lung is examined. The preoperative chest CT scans of 74 patients with pathologically proven squamous cell lung carcinoma were prospectively and retrospectively reviewed. Criteria for the diagnosis of malignant hilar involvement were nonvascular mass enlarging the hilum; local alteration of hilar contour; adenopathy greater than 1 cm; thickened posterior wall of the bronchus intermedius and distal upper lobe bronchi; and bronchial displacement, compression, and obstruction. Criteria for the diagnosis of malignant mediastinal involvement were confluence of tumor with the mediastinum, altered contour of the azygoesophageal recess, thickened posterior wall of the proximal main stem bronchi, and mediastinal adenopathy greater than 1 cm. Calcified hilar and mediastinal nodes were considered benign. Our results, corrected for reader error, were 92% sensitive, 92% specific, and 96% accurate in the hilum and 95% sensitive, 77% specific, and 82% accurate in the mediastinum. These data support a significant role for chest CT in the preoperative staging of non small cell lung carcinoma.

From 1978-1980, 20 patients with radiographically occult squamous cell carcinoma of the lung were admitted to Toronto General Hospital. Among them, five had in situ carcinoma, three had microinvasive carcinoma, and 12 early invasive. All cases were first diagnosed by cytologic examinations of sputum, localized by bronchoscopy, and had been verified histologically. It appears that a cytologic diagnosis of in situ squamous cell carcinoma of the lung could not be established on the basis of a single abnormal squamous cell or an occasional group of abnormal cells, but could be reached by putting together all the cytologic findings observed in the preparations. The criteria for the cytologic diagnosis are elucidated. Cytomorphologically there was no difference between microinvasive and advanced invasive carcinoma. However, in a patient with known localized in situ carcinoma and previous persistent cytologic findings of the same from that particular site, the finding of frankly malignant cells from the same site in the follow-up bronchoscopic examination was almost definitely an indication of microinvasive carcinoma, which usually showed evidence of both in situ and invasive carcinoma in the bronchial brushing specimens. None of the three microinvasive carcinoma cases had positive lymph nodes, but four of the 12 patients with early invasive carcinoma had metastases to the nodes at the time of surgery. Hence, the best time to effectively treat the invasive squamous cell carcinoma of the lung is at the microinvasive stage when the disease is considered curable.

Discrepant reports on the utility of gallium scanning in the preoperative evaluation of patients with lung cancer prompted a prospective study of the test. The authors studied 47 patients with lung cancer who underwent preoperative gallium scanning and frontal tomography of the mediastinum. Both tests were found to be most accurate in predicting the presence of mediastinal metastases among patients with squamous cell carcinoma. Both test may help direct surgical planning in patients with known squamous cell carcinoma of the lung.

Thirteen patients with metastatic squamous cell cancer of the lung were treated, in a nonrandomized study, with an oral high-dose methotrexate and citrovorum factor rescue regimen. There was some response and/or stabilization of disease for at least three months in six (46%) of 13 cases. The median survival time of the study group was double (365 vs. 180 days) that of a retrospectively matched control group. This suggests a possible therapeutic effect of this treatment program in metastatic squamous cell cancer of the lung.

Sixty-seven patients with inoperable squamous cell carcinoma of the lung were randomized to receive spilt-course irradiation therapy, 40 Gy in 10 fractions over 5 weeks plus either placebo or misonidazole 1.200 mg/m2 orally on each treatment day. The target area was the primary tumor, both hilar regions, mediastinum, and both supraclavicular regions. Thirty-three patients received misonidazole, while 34 patients received placebo. Mean observation time for the study was 27 months range, 17–36+ months. 31% of the patients in the misonidazole group obtained a complete response (CR) or a partial response (PR) as compared to 29% in the placebo group. No difference was demonstrated in the relapse pattern comparing the two groups. The death intensity was significantly higher (P = 0.03) in the misonidazole than in the placebo group, with the median survival being 4.2 and 6.7 months, respectively. Eight patients in the misonidazole group (31%) developed sensoric neuropathy while one patient in the placebo group developed irradiation myelopathy of the Brown-Sequard type. The group of patients who later developed neuropathy had significantly higher plasma misonidazole concentrations on treatment days than the group of patients who did not. It is concluded that the combination of misonidazole and irradiation therapy for inoperable squamous cell carcinoma of the lung has no effect on response rate and relapse pattern, but a significant unexplained adverse effect on survival. Cancer 52:20-24, 1983.

The serum level of tumor-antigen 4 (TA-4) was measured in 401 patients with squamous cell carcinoma (SCC) of various organs (76 lung, 82 esophagus, and 234 head and neck). The mean serum level of TA-4 in patients with lung SCC was 3.6 times higher than that in healthy controls and even higher in the advanced stages of disease (III, IV). In patients with benign diseases or other types of lung cancer, however, the TA-4 serum level was not different from the controls regardless of the clinical stage. During radiation therapy, the TA-4 levels in patients with lung SCC decreased with reduction in tumor size. It increased again markedly during recurrence. Similarly, patients with SCC of the esophagus and head and neck also showed elevated TA-4 levels but only at advanced stages and in recurrence. It was concluded that TA-4 is highly related to SCC not only of the uterine cervix but also of other organs and that serum level determinations are useful for monitoring therapeutic effects and recurrence of these diseases, despite some limitations.