Epidermal growth factor receptor expression on oral mucosa dysplastic epithelia and squamous cell carcinomas

Summary The expression of the receptor for epidermal growth factor (EGF) has been determined on oral squamous cell carcinomas. Immunoreactive receptor was localized using a monoclonal anti-EGF-receptor antibody which reacts with sequences in the external domain of the receptor. Frozen sections were studied from 40 patients with squamous cell carcinomas. In 16 sections from the patients with the squamous cell carcinomas, normal differentiated oral mucosa was included and in 7 of these the patients had received preoperative radiotherapy. Sections from 6 other patients with squamous cell carcinoma contained dysplastic epithelia. EGF-receptor-positive cells were present in the basal cell layer on normal differentiated oral mucosa. In sections from patients receiving preoperative radiotherapy the EGF-receptor-positive cells were also found in the spinous cells. In dysplastic epithelia nearly all cells stained for the receptor. The distribution and staining intensity of the EGF receptor varied in the oral squamous cell carcinomas, 36 were positive. The staining pattern in the carcinomas obtained from patients receiving preoperative radiotherapy was not altered qualitatively. Nearly all poorly differentiated cells were stained, but when the tumor was moderately to well differentiated a reduction in the extent of staining in certain areas was seen, paralleling the findings observed in the differentiated upper layers of the normal oral mucosa. This was most pronounced for the epithelial pearls, where the EGF-receptor-positive cells were localized to the undifferentiated cells in the periphery. The results of the present investigation confirm the presence of the EGF receptor on undifferentiated cells, with the extent of the staining reaction on oral squamous cell carcinomas varying inversely with cellular differentiation.     

Expression of epidermal growth factor receptor in laryngeal dysplasia and carcinoma

The immunoreactivity of epidermal growth factor receptor (EGFR) was studied in laryngeal biopsy specimens from 24 patients. The study comprised 5 cases of normal laryngeal mucosa, 5 cases of dysplasia, 7 cases of well differentiated squamous cell carcinoma, and 7 cases of poorly to moderately differentiated squamous cell carcinoma. EGFR was in general not expressed in normal and dysplastic epithelia, whilst all carcinomas showed a rather strong positive immunoreactivity. There was no significant difference in staining patterns between the well and poorly to moderately differentiated carcinomas. The results suggest that EGFR constitutes a component of neoplastic, but probably not preneoplastic, laryngeal disease. The study failed to reveal any difference in staining pattern between different types of laryngeal squamous cell carcinoma.     

Involucrin in laryngeal dysplasia. A marker for differentiation

Involucrin is a major structural subunit of the cross-linked protein envelope that encases keratin in maturing squamous cells. Intracytoplasmic involucrin is identifiable via immunoperoxidase techniques as these cells migrate from the basal layer to the more superficial layers of the stratified epithelium. Normal squamous epithelia and mildly dysplastic epithelia show uniform staining in the suprabasal and superficial layers of the mucosa but show no staining in the basal layer. Moderate to severe dysplasias and invasive carcinomas demonstrate irregular or focal staining in all three layers. Thirty-three microscopic samples from 27 glottic laryngeal biopsy specimens were reviewed. The histochemically abnormal differentiation identified via involucrin staining correlated with accepted histologic criteria for dysplasia. Involucrin staining may provide objective information to assist the pathologist in differentiating degrees of dysplasia in laryngeal biopsy specimens.     

α-甲基酰基辅酶A消旋酶在喉癌中的表达

目的研究α-甲基酰基辅酶A消旋酶(AMACR)在喉癌中的表达,初步探讨AMACR在喉鳞癌生物学行为中的意义。方法用免疫组织化学EliVisionTMplus二步法(福州迈新)检测40例原发喉鳞癌、20例声带息肉及10例癌旁组织中AMACR的表达情况。结果40例喉癌中13例(32.5%)存在不同程度的AMACR表达,在20例声带息肉和10例正常喉组织中无AMACR表达,差异有统计学意义(P<0.01)。AMACR在高分化鳞癌和中、低分化鳞癌中表达的阳性率分别为50%、15%,差异有统计学意义(P<0.05),Ⅰ、Ⅱ期与Ⅲ、Ⅳ期喉癌AMACR阳性率无统计学意义,AMACR表达与性别、肿瘤部位、颈淋巴结转移无统计学意义(P>0.05)。结论AMACR在喉鳞癌中有阳性表达,其表达可能与分化有关,与性别、部位、临床分期、颈淋巴结转移无明显相关性。     

喉鳞状细胞癌中表皮生长因子受体的表达与临床病理特征的关系

为了解喉部鳞状细胞癌中表皮生长因子受体（ＥＧＦ－Ｒ）的表达与临床特征、细胞分化及预后的关系，作者通过免疫组织化学方法（Ｓ－Ｐ法）检测了３６例喉部鳞状细胞癌的石蜡标本，发现２４例出现ＥＧＦ－Ｒ阳性表达，其表达率为６６．７％，作为对照组的２５例喉旁正常组织中只有１例出现ＥＧＦ－Ｒ阳性表达；ＥＧＦ－Ｒ阳性表达与患者的年龄（≤６０岁、〉６０岁）、肿瘤部位无相关性（Ｐ〉０．０５）；而与ＴＮＭ分期、组织分化程     

Immunohistochemical study of dysplasia and squamous cell carcinoma of the larynx

Formalin- or alcohol-fixed, paraffin-embedded laryngeal specimens were stained immunohistochemically with several kinds of monoclonal anti-Keratin antibody (KL-1, PKK-1, PKK-2, PKK-3), polyclonal anti-Keratin antibody, and epithelial membrane antigen. Immunohistochemical technique was used by Avidin-Biotin Complex method with the following subjects; normal epithelium 6 cases, dysplasia 15 cases, inflammation and polyp 12 cases, squamous cell carcinoma 47 cases. 6 specimens of squamous cell carcinoma were totally resected and alcohol-fixed, and other specimens were all biopsied and formalin-fixed. Comparing these two methods, the alcohol-fixed specimen gave superior result to those obtained with formalin-fixed in its staining. Non-staining area was recognized around basal layer by KL-1 stain in the normal epithelium. Enlargement of non-staining area was recognized in the dysplasia. Also, KL-1 staining showed positive staining with the keratinizing squamous cell carcinoma, and weak staining with the non-keratinizing squamous cell carcinoma. And, PKK-3 showed weak staining in the keratinizing squamous cell carcinoma. The results indicate that high molecular weight keratin (56 kilodalton) hardly localize around the basal layer in the squamous epithelium, and also in the non-keratinizing squamous cell carcinoma. The other way, this also suggests that low molecular weight keratin (45 kilodalton) hardly localize in the keratinizing squamous cell carcinoma. It is supposed that intracellular localization of keratin of dysplastic epithelium and squamous cell carcinoma varies from that in the normal squamous epithelium. Accordingly, monoclonal keratin stain is thought to be an useful method for the diagnosis of dysplasia and squamous cell carcinoma.     

Immunohistochemical investigation on expression of cytokeratins in normal epithelium, precancerous lesions and carcinomas of the hypopharynx]

In order to obtain a more objective method to evaluate epithelial disorders and carcinomas of the hypopharynx, the expression pattern of cytokeratins (CKs) was investigated by ABC technique using several kinds of monoclonal antibodies that react monospecifically with each subclass of CKs. In normal epithelia, CK-19 was strongly positive in the basal layer but apparently reduced in suprabasal layers and completely negative in superficial layers, while CK-13 showed a striking contrast to CK-19, being expressed within the whole thickness of epithelia except only in the basal layer. These 2 subclasses were also observed in "abnormal" epithelia, and characteristic changes of their combination were demonstrated in proportion to the histological gradings. In invasive carcinomas, CK-19 was strongly positive in all carcinoma cells of poorly differentiated carcinomas. It was sporadically positive in moderately differentiated carcinomas, the more differentiated the more sporadic. It was completely negative in well differentiated carcinomas. CK-13, on the other hand, was negative in poorly differentiated carcinomas but positive in keratinized cells of moderately or well differentiated carcinomas. Strong expression of CK-1 was observed only in well keratinized cells of hyperkeratotic epithelia and well differentiated carcinomas. These characteristic findings are consistently observed in all samples and, then, may be useful in evaluating epithelial disorders and carcinomas of the hypopharynx, when used in conjunction with standard histological techniques. It seems most likely that these results play a part in investigating normal and abnormal processes of cell differentiation.     

Immunohistochemical detection of glutathione S-transferase (GST) -pi in head and neck carcinoma and its changes by radiotherapy]

It is well known that the "placental form of glutathione S-transferase" (GST-pi) is present in high concentrations in most human carcinomas. However, its expression in head and neck carcinomas have not yet been reported. The author investigated the expression of GST-pi in the tissue of pharyngeal and laryngeal carcinomas by the immunohistochemical procedure, and the following results were obtained: 1) GST-pi was positive in 80% of laryngeal carcinomas (35 cases) and 52.8% of pharyngeal carcinomas (36 cases). As a rule, well differentiated squamous cell carcinomas showed stronger expression of GST-pi than poorly differentiated squamous cell carcinomas. 2) Although normal epithelia of the pharynx and larynx showed negative GST-pi, it should be noticed that 54.6% of precancerous epithelia (11 cases) showed positive GST-pi. 3) Most patients treated with radiotherapy showed the diminution of GST-pi expression after the irradiation. However, co-relation between the strength of initial GST-pi expression and the effectiveness of radiotherapy was not observed (p < 0.01).     

细胞周期调控因子与喉癌癌变的相关性研究

目的 :探讨喉癌癌变过程中 Cyclin E、p2 1WAF1 /CIP1和 p5 3表达的临床病理学意义。方法 :用免疫组化检测 2 0例喉正常粘膜、40例喉不典型增生病变和 6 0例喉癌组织中 Cyclin E、p2 1WAF 1 /CIP1和 p5 3的表达。结果 :1Cyclin E阳性表达率在正常组、不典型增生组和喉癌组分别为 5 .0 % (1/ 2 0 )、2 0 .0 % (8/ 40 )、45 .0 % (2 7/ 6 0 ) ,喉癌组与正常组比较 ,其差异有极显著性意义 (P<0 .0 1) ;p2 1WAF1 /CIP1阳性表达率分别为 95 .0 % (19/ 2 0 )、75 .0 % (30 /40 )和 6 3.3% (38/ 6 0 ) ,喉癌组与正常组比较 ,其差异亦有显著性意义 (P<0 .0 5 ) ;p5 3阳性表达率分别为 0 (0 /2 0 )、30 .0 % (12 / 40 )和 6 1.7% (37/ 6 0 ) ,喉癌组与正常组比较 ,其差异有极显著性意义 (P <0 .0 1)。 2 p2 1WAF 1 /CIP1在高、中、低分化的喉癌中阳性表达率逐渐降低 ,其差异有显著性意义 (P <0 .0 5 )。 3 Cyclin E和 p5 3阳性表达显著相关 ,p2 1WAF 1 /CIP1与 p5 3阳性表达无相关性。结论 :1Cyclin E和 p5 3异常表达是喉癌发生中早期分子事件。 2p2 1WAF 1 /CIP1 表达与喉癌细胞分化程度有关。 3细胞周期因子相互调控机制在喉癌发展中起重要作用。     

Expression of gap junction proteins (connexin 26, 30, 32, 43) in normal mucosa,hyperkeratosis and carcinoma of the human larynx

INTRODUCTION: Gap junction proteins (connexins = Cx) form transmembrane channels and mediate the transfer of small molecules and ions between the cytoplasm of adjacent cells. Most tissues express several Cx isoforms. The precise combination might play an important role in the maintenance of cell differentiation. Human carcinogenesis is accompanied by aberrant expression and function of Cx. While the larynx is a target organ for many tumor promoters, no data on Cx expression in laryngeal mucosa are available. The goal of the study was to observe the expression of different Cx (Cx26, -30, -32 and -43) in the normal mucosa, hyperkeratoses and carcinomas of the human larynx. METHOD: The immunofluorescence method was performed in normal (n = 7) and dysplastic (n = 6) laryngeal mucosa and in squamous cell carcinoma (n = 7) using affinity-purified polyclonal rabbit antibodies against the 4 Cx isoforms and FITC-conjugated secondary antibodies. RESULTS: The immunofluorescence staining of the normal human vocal fold's epithelium showed the expression of Cx26 and Cx30 in the parabasal and intermediate layers, whereas Cx43 was localized in the basal, parabasal and lower intermediate layers. Cx epitopes could not be found in the upper layers. The precanceroses showed a similar expression of the Cx compared to normal laryngeal epithelium. Due to the higher degree of staining observed in dysplastic specimens, a hyperexpression of Cx26, -30 and -43 could be assumed. The squamous cell carcinomas were characterized by inhomogeneous staining for Cx26, -30 and -43. Regions of intensive expression alternated with regions of no expression. Cx32 could not be observed by immunofluorescence staining in laryngeal tissue. CONCLUSION: In immunohistochemical terms, there was no alteration of the expression of Cx isoforms during carcinogenesis in the laryngeal epithelium. These results do not exclude a loss of functional intercellular gap junction communication by posttranslational modifications of Cx isoforms or disturbed Cx integration into the gap junction channel. Further studies should investigate potential defective gap junctional intercellular communication in cancer cells based on molecular studies.     

Relationship among lymphatic metastasis, pericancerous lymphocytic reaction and dendritic cell infiltration in laryngeal carcinoma cells]

OBJECTIVE: To study the role and the clinical significance of dendritic cell infiltration against tumor cells in patients with laryngeal squamous cell carcinoma. METHODS: Immunohistochemical method using S-100 protein antibody was employed to detect dendritic cells (DC) on paraffin-embedded tissue sections from 23 patients with laryngeal squamous cell carcinomas. The relationships among the density of dendritic cell infiltration in laryngeal carcinomas and cervical lymphatic metastasis, pericancerous lymphocytic reaction and other clinicopathologic parameters were observed. RESULTS: The numbers of dendritic cells infiltrating among laryngeal carcinoma cells in patients with no cervical lymph metastasis was significantly larger than those with cervical lymphatic metastasis (t = 4.889, P < 0.01). Significant increase DC infiltration among laryngeal carcinoma cells was found in the group with intensively positive reaction of pericancerous lymphocyte than in the medium and weakly positive groups. The number of infiltrating dendritic cells in patients who had survived more than 5 years was significantly larger than those survived less than 5 years (t = 4.423, P < 0.01). The numbers of the infiltrating dendritic cells in patients with well-differentiated squamous cell carcinoma and poorly differentiated squamous cells carcinoma were 2.2 +/- 1.07 and 14.6 +/- 7.14 respectively, which were significantly different (q = 4.532, P < 0.05). CONCLUSION: The study showed that DC infiltration among laryngeal squamous carcinoma cells played an important role in the host immune reaction against tumor. It indicated that when the density of infiltrating DC is higher, the patients had less chance of cervical lymph metastasis and may have a longer survival time. There was a coordinative effect between DC infiltration in tumor cells and pericancerous lymphocyte reaction. Thus, the DC infiltration among laryngeal squamous cells could be used as an index of prognosis.     

凋亡抑制蛋白XIAP在喉鳞状细胞癌中的表达及其临床病理学意义

目的:探讨调亡抑制蛋白XIAP在喉癌中的表达情况,了解其与喉癌临床生物学行为的关系。方法:选择喉鳞状细胞癌患者50例,术前均未进行化学和放射治疗。采用免疫组织化学方法染色(SP法),检测XI-AP蛋白在喉癌和喉正常黏膜组织中的表达及其与临床病理参数之间的关系。结果:XIAP蛋白主要表达在肿瘤细胞细胞质和细胞核,为粗细不一的棕黄至棕黑色颗粒。XIAP在喉鳞状细胞癌中的表达与正常喉黏膜比较,前者表达显着增高,差异有统计学意义(P<0.01)。XIAP蛋白阳性表达与患者年龄、性别、吸烟史、肿瘤生长部位及有无淋巴结转移无相关性,而与临床分期、T分期及病理分级有关(均P<0.05)。结论:XIAP蛋白在喉正常组织中低表达,而在喉癌中高表达。XIAP蛋白的表达程度与肿瘤临床病理特征有关。XIAP在喉癌发生、发展过程中可能具有重要作用。     

Basement membrane components in normal, dysplastic, neoplastic laryngeal tissue and metastatic lymph nodes

The immunohistochemical localization of the basement membrane (BM) components laminin, type IV collagen and fibronectin was analyzed in normal, dysplastic and neoplastic laryngeal specimens. The distribution of these macromolecules was also investigated in metastatic lymph nodes. A regular and continuous staining for laminin and type IV collagen was present in normal and mild dysplastic epithelium (LIN I); interruptions and reduplications were more evident in severe dysplasia (LIN III), together with an increased positivity for fibronectin in the subepithelial connective tissue. In squamous cell carcinomas the distribution of BM components was related to the degree of cellular differentiation, with a decreased immunostaining being evident in moderately and poorly differentiated carcinomas. Furthermore, the positivity for laminin and type IV collagen was influenced by the pattern of neoplastic growth, being continuous around the "pushing" border and discontinuous where the neoplastic front had an "invading" appearance. Similar changes were present in cervical metastatic lymph nodes. These observations tend to support the theory that the neoplastic growth is a cyclic process, with BM component synthesis and reabsorbtion related to the shifts of cellular metabolism.     

Overexpression of scatter factor and its receptor (c-met) in oral squamous cell carcinoma

Hypothesis: Scatter factor (SF) is a pleiotropic growth factor that recently has been shown to induce epithelial cell proliferation, random motility, and invasion via interaction with its receptor, a tyrosine kinase encoded by the c-met proto-oncogene. Studies involving a variety of solid tumors have suggested that overexpression of the SF/c-met ligand-receptor pair is associated with the acquisition of a malignant phenotype. We hypothesize that SF and c-met are overexpressed in epithelial malignancies of the head and neck including squamous cell carcinoma (SCC) of the oral cavity. Study Design: Immunohistochemical staining of randomly selected normal, dysplastic, and malignant oral tissues. Methods: Formalin-fixed, paraffin-embedded tissues were obtained from the Department of Oral Pathology at Shands Hospital (University of Florida), Gainesville, Florida. Examples of mild dysplasia, severe dysplasia, well-differentiated SCC, moderately differentiated SCC, and poorly differentiated SCC were randomly selected from the dictated reports of one of two staff oral pathologists. Histologically normal margins of each specimen served as normal controls. The tissues were immunohistochemically stained using commercially available antibodies against SF and c-met. Appropriate negative controls were run with each batch to ensure staining specificity. Evaluation of staining intensity was carried out using a computerized image analysis system. A one-way analysis of variance (ANOVA) with pairwise multiple-comparison procedures (Fisher method) was used to analyze the data. Results: Statistically significant differences (P < .0001) in the intensity of staining were noted between the malignant and normal and the malignant and dysplastic tissues for both SF and c-met. No differences were appreciated when staining of normal and dysplastic sections of the SF-stained tissue were compared. Conclusions: The results suggest that the SF/c-met ligand-receptor pair is overexpressed in SCC of the oral cavity.     

Immunohistochemical identification of squamous carcinoma of the head and neck with monoclonal antibody SQM1

Frozen tissue sections of biopsies from head and neck squamous cancer lesions were examined for immunohistochemical staining with a recently developed monoclonal antibody, designated as SQM1 antibody and directed against the surface membrane of squamous carcinoma cells. SQM1 antibody stained selectively squamous carcinoma, while normal mucosa and cells of the stroma were non-reactive. Positive staining of tumor was found in 33/35 specimens obtained from several major sites of the head and neck area and was observed in primary manifestations and lymph node metastases as well as in recurrences. The most consistent reactivity was seen with carcinomas of the tongue. Well differentiated squamous carcinomas contained a higher proportion of SQM1 positive tumor cells than poorly differentiated carcinomas. We suggest that the SQM1 antibody may aid in the immunohistochemical identification of squamous carcinoma of the head and neck area.     

Guanylate cyclase activity in normal and neoplastic squamous epithelia from the upper aero-digestive tract

Cyclic nucleotides (cAMP, cGMP) are suggested to participate in the regulation of cell growth and differentiation. Guanylate cyclase is the enzyme which catalyzes the synthesis of cGMP. The basal guanylate cyclase activity was slightly higher in well-differentiated squamous cell carcinomas than in normal mucosa, but was two-fold higher in papillomas. Poorly differentiated squamous cell carcinoma did not show any increased basal activity. Stimulation with nitroprusside (NP) resulted in a 20% increased activity for normal mucosa and a 30% increase for poorly differentiated carcinomas, whereas enzyme prepared from well-differentiated squamous carcinomas and papillomas showed a two-fold increase.     

喉鳞状细胞表皮生长因子受体mRNA的表达及其意义

目的：了解喉部鳞状细胞表皮生长因子受体（ＥＧＦ－Ｒ）ｍＲＮＡ的表达情况及其与喉部鳞癌的特征，组织分化的关系。方法；用斑点杂交法检测２０例喉鳞状细胞癌活体标本。结果：１５例出现ＥＧＦ－Ｒ ｍＲＮＡ表达，其表达率为７５Ａ％。ＥＧＦ－Ｒ ｍＲＮＡ表达与患者年龄，肿瘤的部位无关；而与ＴＮＭ分期，组织分化程度有关，Ｔ３，Ｔ４期的表达高于Ｔ１，Ｔ２期；分化程度低的肿瘤，其ＥＧＦ－Ｒ ｍＲＮＡ表达高于分化程度中     

Cytokeratin 18 expression in squamous cell carcinoma of the head and neck

Cytokeratin (CK) expression was studied in squamous cell carcinomas of different subsites in the head and neck by using cryostat sections from 27 head and neck squamous cell carcinomas (HNSCCs) and 6 cell lines established from HNSCC. All tissues were analyzed immunohistochemically with a panel of monospecific anti-keratin monoclonal antibodies. Most carcinomas recapitulated the expression pattern of keratins present in the basal layer of normal epithelium from the site of tumor origin. Regional differences in the expression of simple-epithelial type of keratins in stratified (pseudostratified) epithelia were to a large extent repeated in corresponding carcinomas. In the present study, localization of various keratins were surveyed and CK 18 specific monoclonal antibodies were specifically used to distinguish SCCs of the larynx or hypopharynx from SCCs of the oral cavity. CK 18 staining of almost all tumor cells was detected in 11 of 12 SCCs of the larynx and hypopharynx, but was only detected sporadically in 3 of 9 SCCs of the oral cavity. The present results show that CK 18 typing might be useful for distinguishing sites of origin of various HNSCCs. Findings also indicate that CK 18 expression in SCC might be modulated by microenvironmental factors.     

Lectin-binding patterns and cell kinetics of head and neck squamous cell carcinomas

In order to elucidate the cell characteristics of head and neck squamous cell carcinomas, the cell kinetics and lectin binding patterns were compared with the histological classification and staging of the tumors, using surgically resected materials (maxillary sinus 10, oral cavity 21, pharynx 8, larynx 11). Eight biotinylated lectins (WGA, 1-PHA, ConA, UEA1, RCA1, SBA, DBA, PNA) were applied to the paraffin-embedded sections, and were visualized histochemically by the streptavidin-alkaline phosphatase method. The DNA contents of the isolated carcinoma cells obtained from the adjacent thick sections were evaluated using an epi-illumination cytofluorometer after propidium iodide staining. On lectin histochemistry, the binding pattern of WGA lectin was similar between carcinoma tissues and normal tissues, but the binding was more intense in well differentiated than less differentiated carcinomas. Lymph node metastasis was found to be related to the presence of cells with poor WGA-binding. In the binding patterns of the other lectins, RCA1, SBA and ConA were related to the differentiation of carcinomas, but they were not related to the TNM-classification. DNA cytofluorometry exhibited marked polyploidization, which progressed with the advancement of the clinical and pathological staging of carcinomas. However, the DNA ploidy pattern was not associated with the cell characteristics such as the degree of histological differentiation and the lectin-binding pattern, except that the appearance of aneuploidy had some relationship with the binding-patterns of UEA1 and 1-PHA.     

T-淋巴细胞成熟相关性蛋白基因在正常喉黏膜和喉良性病变及喉癌中的表达和意义

目的：研究MAL在正常喉黏膜组织、声带息肉、喉不典型增生组织及喉癌中表达进而分析其不同分布的意义。方法：运用免疫组织化学的方法检测MAL在正常喉黏膜组织、声带息肉、喉不典型增生组织及喉癌中分布情况。结果：MAL在正常喉黏膜组织中存在表达。比较正常喉黏膜组织和声带息肉组织,MAL表达情况无明显差异。比较正常喉黏膜组织、喉不典型增生及喉癌,MAL在喉不典型增生和喉癌中均表达下调,MAL在喉鳞状细胞癌中表达较喉不典型增生中明显下调。结论：MAL存在正常喉黏膜组织中,在癌变早期时因细胞功能变化而发生表达改变。可作为喉鳞状细胞癌早期诊断的指标之一。